West Kazakhstan Medical Journal
ISSN: 2707-6180 (Print) 2707-6199 (Online)
Pioneering research advancing the frontiers of medical knowledge and healthcare practices.
New Horizons in Treatment of Knee Osteoarthritis: A Brief Look-up at Emerging Approaches
Published date: Dec 21 2023
Journal Title: West Kazakhstan Medical Journal
Issue title: West Kazakhstan Medical Journal: Volume 65 Issue 4
Pages: 4–43
Authors:
Abstract:
Knee osteoarthritis (OA) is a chronic and prevalent musculoskeletal condition that is the underlying cause of disability in most patients worldwide. Even though the pathophysiology of KOA has not yet been fully understood and includes a wide range of risk factors, current therapeutic options are temporarily palliative rather than curative. In recent years, new strategies have focused on the curative agents. As part of this review, we highlight the latest treatment approaches for KOA.
References:
[1] Huang XY, Wang ZY, Wang HY, Chen D, Tong LP. Novel strategies for the treatment of osteoarthritis based on biomaterials and critical molecular signaling. J Mater Sci Technol. 2023;149:42-55.
[2] Primorac D, Molnar V, Rod E, Jelec Z, Cukelj F, Matisic V, et al. Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations. Genes. 2020;11(8):854.
[3] Arya R, Jain V. Osteoarthritis of the knee joint: An overview. JIACM. 2013;14(2):154-62.
[4] Mazzuca SA, Brandt KD, Buckwalter KA. Detection of radiographic joint space narrowing in subjects with knee osteoarthritis: longitudinal comparison of the metatarsophalangeal and semiflexed anteroposterior views. Arthritis Rheum. 2003;48(2):385-90.
[5] Crawford DC, Miller LE, Block JE. Conservative management of symptomatic knee osteoarthritis: a flawed strategy? Orthop Rev (Pavia). 2013;5(1):e2.
[6] Lespasio MJ, Piuzzi NS, Husni ME, Muschler GF, Guarino A, Mont MA. Knee Osteoarthritis: A Primer. Perm J. 2017;21:16-183.
[7] Binvignat M, Pedoia V, Butte AJ, Louati K, Klatzmann D, Berenbaum F, et al. Use of machine learning in osteoarthritis research: a systematic literature review. RMD Open. 2022;8(1):e001998.
[8] Bao C, He C. The role and therapeutic potential of MSC-derived exosomes in osteoarthritis. Arch Biochem Biophys. 2021;710:109002.
[9] Mianehsaz E, Mirzaei HR, Mahjoubin-Tehran M, Rezaee A, Sahebnasagh R, Pourhanifeh MH, et al. Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis? Stem Cell Res Ther. 2019;10(1):340.
[10] Wang X, Wei L, Lv Z, Zhao B, Duan Z, Wu W, et al. Proximal fibular osteotomy: a new surgery for pain relief and improvement of joint function in patients with knee osteoarthritis. J Int Med Res. 2017;45(1):282-9.
[11] Peng H, Ou A, Huang X, Wang C, Wang L, Yu T, et al. Osteotomy Around the Knee: The Surgical Treatment of Osteoarthritis. Orthop Surg. 2021;13(5):1465-73.
[12] He Y, Li Z, Alexander PG, Ocasio-Nieves BD, Yocum L, Lin H, et al. Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models. Biology-Basel. 2020;9(8).
[13] Zeng C, Bennell K, Yang Z, Nguyen UDT, Lu N, Wei J, et al. Risk of venous thromboembolism in knee, hip and hand osteoarthritis: a general population-based cohort study. Ann Rheum Dis. 2020;79(12):1616-24.
[14] Wen C, Xiao G. Advances in osteoarthritis research in 2021 and beyond. J Orthop Translat. 2022;32:A1-A2.
[15] Safiri S, Kolahi AA, Smith E, Hill C, Bettampadi D, Mansournia MA, et al. Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017. Ann Rheum Dis. 2020;79(6):819-28.
[16] Jin ZY, Zhao JK, Sun LY. Response to: ’Correspondence on ’Incidence trend of five common musculoskeletal disorders from 1990 to 2017 at the global, regional and national level: results from the Global Burden of Disease study 2017’ by Chiang. Ann Rheum Dis. 2023;82(2):e47-e.
[17] Berenbaum F. Annals of the Rheumatic Diseases collection on osteoarthritis (2018– 2023): hopes and disappointments. Ann Rheum Dis. 2023.
[18] Coaccioli S, Sarzi-Puttini P, Zis P, Rinonapoli G, Varrassi G. Osteoarthritis: New Insight on Its Pathophysiology. J Clin Med. 2022;11(20):6013.
[19] Alkady EA, Selim ZI, Abdelaziz MM, El-Hafeez FA. Epidemiology and socioeconomic burden of osteoarthritis. J Current Med Res Opinion. 2023;8(1):7-11.
[20] Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020;29-30:100587.
[21] Mody G, Woolf A. A report on the global burden musculoskeletal disorders. Business briefing of European Pharmacotherapy Association. BMJ Open. 2003;12(6):e062183.
[22] Szilagyi IA, Waarsing JH, Schiphof D, van Meurs JBJ, Bierma-Zeinstra SMA. Towards sex-specific osteoarthritis risk models: evaluation of risk factors for knee osteoarthritis in males and females. Rheumatology. 2022;61(2):648-57.
[23] Zhakhina G, Gusmanov A, Sakko Y, Yerdessov S, Semenova Y, Saginova D, et al. The Regional Burden and Disability-Adjusted Life Years of Knee Osteoarthritis in Kazakhstan 2014-2020. Biomedicines. 2023;11(1):216.
[24] Mahir L, Belhaj K, Zahi S, Azanmasso H, Lmidmani F, El Fatimi A. Impact of knee osteoarthritis on the quality of life. Ann Phys Rehabil Med. 2016;59:e159.
[25] Ringdahl E, Pandit S. Treatment of knee osteoarthritis. Am Fam Physician. 2011;83(11):1287-92.
[26] Michael JW, Schluter-Brust KU, Eysel P. The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch Arztebl Int. 2010;107(9):152-62.
[27] Hsu KY, Tsai YF, Yeh WL, Chen DW, Chen CY, Wang YW. Triggers and decisionmaking patterns for receiving total knee arthroplasty among older adults with knee osteoarthritis: A qualitative descriptive study. J Clin Nurs. 2018;27(23-24):4373-80.
[28] Rankothgedera S, Atukorala I, Fernando C, Munidasa D, Wijayaratne L, Udagama P. A potential diagnostic serum immunological marker panel to differentiate between primary and secondary knee osteoarthritis. PLoS One. 2021;16(9):e0257507.
[29] Rauf KZ A, BW N, Fauzlie Y M. Treating the 5th Vital Sign: A Case of Bilateral Knee Osteoarthritis in a Patient With Childhood Rickets and Systemic Lupus Erythematosus Undergoing Total Knee Arthroplasty. Malaysian J Med Health Sci. 2021;17:125-7.
[30] Anari H, Enteshari-Moghaddam A, Abdolzadeh Y. Association between serum Vitamin D deficiency and Knee Osteoarthritis. Mediterr J Rheumatol. 2019;30(4):216- 9.
[31] Cai C, Hu W, Chu T. Interplay Between Iron Overload and Osteoarthritis: Clinical Significance and Cellular Mechanisms. Front Cell Dev Biol. 2021;9:817104.
[32] Han BK, Kim W, Niu J, Basnyat S, Barshay V, Gaughan JP, et al. Association of Chondrocalcinosis in Knee Joints With Pain and Synovitis: Data From the Osteoarthritis Initiative. Arthritis Care Res (Hoboken). 2017;69(11):1651-8.
[33] Jasper J, Metsaars W, Jansen J. Ochronosis of the knee with secondary osteoarthritis requiring total knee replacement in a patient with cryptogenic organising pneumonia. BMJ Case Rep. 2016;2016.
[34] Aslan B, Erdogan H, Yazisiz V. The view of joints in the Wilson’s disease. Eur J Rheumatol. 2020;7(4):205-6.
[35] Kido J, Matsumoto S, Sugawara K, Nakamura K. Wilson disease developing osteoarthritic pain in severe acute liver failure: A case report. World J Hepatol. 2019;11(7):607-12.
[36] Howard RG, Samuels J, Gyftopoulos S, Krasnokutsky S, Leung J, Swearingen CJ, et al. Presence of gout is associated with increased prevalence and severity of knee osteoarthritis among older men: results of a pilot study. J Clin Rheumatol. 2015;21(2):63-71.
[37] Yoo Y, Seo YJ, Huh M, Yoo JH, Yun KH, Kim SJ. Gout and coexisting pseudogout in the knee joint. Knee Surg Sports Traumatol Arthrosc. 2011;19(4):553-5.
[38] Pelsma ICM, Kroon HM, van Trigt VR, Pereira AM, Kloppenburg M, Biermasz NR, et al. Clinical and radiographic assessment of peripheral joints in controlled acromegaly. Pituitary. 2022;25(4):622-35.
[39] Mohammed A, Alshamarri T, Adeyeye T, Lazariu V, McNutt LA, Carpenter DO. A comparison of risk factors for osteo- and rheumatoid arthritis using NHANES data. Prev Med Rep. 2020;20:101242.
[40] Rodriguez-Merchan EC, Valentino LA. Orthopedic disorders of the knee in hemophilia: A current concept review. World J Orthop. 2016;7(6):370-5.
[41] Helliwell PS. Osteoarthritis and Paget’s disease. Br J Rheumatol. 1995;34(11):1061-3.
[42] Popat R, Tsitskaris K, Millington S, Dawson-Bowling S, Hanna SA. Total knee arthroplasty in patients with Paget’s disease of bone: A systematic review. World J Orthop. 2018;9(10):229-34.
[43] Ferreira TFA, Dos Santos APT, Leal AS, de Araujo Pereira G, Silva SS, Moraes- Souza H. Chronic osteo-articular changes in patients with sickle cell disease. Adv Rheumatol. 2021;61(1):11.
[44] Manlapaz DG, Sole G, Jayakaran P, Chapple CM. Risk Factors for Falls in Adults with Knee Osteoarthritis: A Systematic Review. PM R. 2019;11(7):745-57.
[45] Hulshof CTJ, Colosio C, Daams JG, Ivanov ID, Prakash KC, Kuijer P, et al. WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of exposure to occupational ergonomic risk factors and of the effect of exposure to occupational ergonomic risk factors on osteoarthritis of hip or knee and selected other musculoskeletal diseases. Environ Int. 2019;125:554-66.
[46] Giorgino R, Albano D, Fusco S, Peretti GM, Mangiavini L, Messina C. Knee osteoarthritis: epidemiology, pathogenesis, and mesenchymal stem cells: what else is new? An update. Int J Mol Sci. 2023;24(7):6405.
[47] Fransen M, Bridgett L, March L, Hoy D, Penserga E, Brooks P. The epidemiology of osteoarthritis in Asia. Int J Rheum Dis. 2011;14(2):113-21.
[48] Loeser RF. Aging processes and the development of osteoarthritis. Curr Opin Rheumatol. 2013;25(1):108-13.
[49] Hame SL, Alexander RA. Knee osteoarthritis in women. Curr Rev Musculoskelet Med. 2013;6(2):182-7.
[50] Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D. Genetic influences on osteoarthritis in women: a twin study. BMJ. 1996;312(7036):940-3.
[51] Yucesoy B, Charles LE, Baker B, Burchfiel CM. Occupational and genetic risk factors for osteoarthritis: a review. Work. 2015;50(2):261-73.
[52] Piva SR, Susko AM, Khoja SS, Josbeno DA, Fitzgerald GK, Toledo FG. Links between osteoarthritis and diabetes: implications for management from a physical activity perspective. Clin Geriatr Med. 2015;31(1):67-87, viii.
[53] Sims R, van der Lee SJ, Naj AC, Bellenguez C, Badarinarayan N, Jakobsdottir J, et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet. 2017;49(9):1373-84.
[54] Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, et al. Genetic metaanalysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet. 2019;51(3):414-30.
[55] Khan NM, Haqqi TM. Epigenetics in osteoarthritis: Potential of HDAC inhibitors as therapeutics. Pharmacol Res. 2018;128:73-9.
[56] Deng Z, Jia Y, Liu H, He M, Yang Y, Xiao W, et al. RhoA/ROCK pathway: implication in osteoarthritis and therapeutic targets. Am J Transl Res. 2019;11(9):5324-31.
[57] Kang M, Ren MP, Li Y, Fu YQ, Deng MM, Li CP. Exosome-mediated transfer of lncRNA PART1 induces gefitinib resistance in esophageal squamous cell carcinoma via functioning as a competing endogenous RNA (Retracted article. See vol. 42, 2023). J Exp Clin Cancer Res. 2018;37:1-16.
[58] Zhang YM, Wang J, Liu XG. Association between hypertension and risk of knee osteoarthritis: A meta-analysis of observational studies. Medicine. 2017;96(32):e7584.
[59] Xing X, Wang Y, Pan F, Cai G. Osteoarthritis and risk of type 2 diabetes: A two-sample Mendelian randomization analysis. J Diabetes. 2023;15(11):987-93.
[60] Park JY, Chung YJ, Song JY, Kim C, Lee H, Son Y, et al. Body Composition and Bone Mineral Density in Postmenopausal Women with Advanced Knee Osteoarthritis Undergoing Surgical Treatment. J Menopausal Med. 2023;29(2):51-7.
[61] Cicuttini FM, Proietto J, Lim YZ. Our biology working against us in obesity: A narrative review on implications for management of osteoarthritis. Osteoarthr Cartil Open. 2023;5(4):100407.
[62] Chen JR, Chen JQ, Hu JC, Huang RS, Shen L, Gu H, et al. Cigarette smoking is linked to an increased risk of delirium following arthroplasty in patients suffering from osteoarthritic pain. CNS Neurosci Ther. 2023;29(12):3854-62.
[63] Geng R, Li J, Yu C, Zhang C, Chen F, Chen J, et al. Knee osteoarthritis: Current status and research progress in treatment (Review). Exp Ther Med. 2023;26(4):481.
[64] Zhang JF, Song LH, Wei JN, Zhang AL, Dong HY, Wen HY, et al. Prevalence of and risk factors for the occurrence of symptomatic osteoarthritis in rural regions of Shanxi Province, China. Int J Rheum Dis. 2016;19(8):781-9.
[65] Vennu V, Abdulrahman TA, Alenazi AM, Bindawas SM. Annual income, age, marital status, and smoking influence healthcare access among American minorities and Caucasians with knee osteoarthritis. Int J Healthcare Man. 2023:1-9.
[66] Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res. 2016;11(1):19.
[67] Brown TD, Johnston RC, Saltzman CL, Marsh JL, Buckwalter JA. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20(10):739-44.
[68] Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494-502.
[69] Zhang W, Doherty M, Peat G, Bierma-Zeinstra MA, Arden NK, Bresnihan B, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis. 2010;69(3):483-9.
[70] Sharma L. Osteoarthritis of the knee. N Engl J Med. 2021;384(1):51-9.
[71] Martel-Pelletier J, Paiement P, Pelletier JP. Magnetic resonance imaging assessments for knee segmentation and their use in combination with machine/deep learning aspredictors of early osteoarthritis diagnosis and prognosis. Ther Adv Musculoskelet Dis. 2023;15:1759720X231165560.
[72] Neogi T, Bowes MA, Niu J, De Souza KM, Vincent GR, Goggins J, et al. Magnetic resonance imaging-based three-dimensional bone shape of the knee predicts onset of knee osteoarthritis: data from the osteoarthritis initiative. Arthritis Rheum. 2013;65(8):2048-58.
[73] Teoh YX, Lai KW, Usman J, Goh SL, Mohafez H, Hasikin K, et al. Discovering Knee Osteoarthritis Imaging Features for Diagnosis and Prognosis: Review of Manual Imaging Grading and Machine Learning Approaches. J Healthc Eng. 2022;2022:4138666.
[74] Kokkotis C, Moustakidis S, Papageorgiou E, Giakas G, Tsaopoulos DE. Machine learning in knee osteoarthritis: A review. Osteoarthr Cartil Open. 2020;2(3):100069.
[75] Abramoff B, Caldera FE. Osteoarthritis: Pathology, Diagnosis, and Treatment Options. Med Clin North Am. 2020;104(2):293-311.
[76] van den Bosch MHJ. Osteoarthritis year in review 2020: biology. Osteoarthritis Cartilage. 2021;29(2):143-50.
[77] Zahan OM, Serban O, Gherman C, Fodor D. The evaluation of oxidative stress in osteoarthritis. Med Pharm Rep. 2020;93(1):12-22.
[78] Kulkarni P, Martson A, Vidya R, Chitnavis S, Harsulkar A. Pathophysiological landscape of osteoarthritis. Adv Clin Chem. 2021;100:37-90.
[79] Barreto G, Manninen M, K KE. Osteoarthritis and Toll-Like Receptors: When Innate Immunity Meets Chondrocyte Apoptosis. Biology-Basel. 2020;9(4):65.
[80] Haseeb A, Haqqi TM. Immunopathogenesis of osteoarthritis. Clin Immunol. 2013;146(3):185-96.
[81] Walsh DA, Bonnet CS, Turner EL, Wilson D, Situ M, McWilliams DF. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. Osteoarthritis Cartilage. 2007;15(7):743-51.
[82] van Lent PL, Blom AB, van der Kraan P, Holthuysen AE, Vitters E, van Rooijen N, et al. Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation. Arthritis Rheum. 2004;50(1):103-11.
[83] Blom AB, van Lent PL, Libregts S, Holthuysen AE, van der Kraan PM, van Rooijen N, et al. Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 2007;56(1):147-57.
[84] Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanasesmatrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther. 2006;8(6):R187.
[85] Onuma H, Masuko-Hongo K, Yuan G, Sakata M, Nakamura H, Kato T, et al. Expression of the anaphylatoxin receptor C5aR (CD88) by human articular chondrocytes. Rheumatol Int. 2002;22(2):52-5.
[86] Moskowitz RW, Kresina TF. Immunofluorescent analysis of experimental osteoarthritic cartilage and synovium: evidence for selective deposition of immunoglobulin and complement in cartilaginous tissues. J Rheumatol. 1986;13(2):391-6.
[87] Chadjichristos C, Ghayor C, Kypriotou M, Martin G, Renard E, Ala-Kokko L, et al. Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes. J Biol Chem. 2003;278(41):39762-72.
[88] Silvestri T, Pulsatelli L, Dolzani P, Frizziero L, Facchini A, Meliconi R. In vivo expression of inflammatory cytokine receptors in the joint compartments of patients with arthritis. Rheumatol Int. 2006;26(4):360-8.
[89] Poree B, Kypriotou M, Chadjichristos C, Beauchef G, Renard E, Legendre F, et al. Interleukin-6 (IL-6) and/or soluble IL-6 receptor down-regulation of human type II collagen gene expression in articular chondrocytes requires a decrease of Sp1.Sp3 ratio and of the binding activity of both factors to the COL2A1 promoter. J Biol Chem. 2008;283(8):4850-65.
[90] Sallusto F, Mackay CR, Lanzavecchia A. The role of chemokine receptors in primary, effector, and memory immune responses. Annu Rev Immunol. 2000;18:593-620.
[91] Ishii H, Tanaka H, Katoh K, Nakamura H, Nagashima M, Yoshino S. Characterization of infiltrating T cells and Th1/Th2-type cytokines in the synovium of patients with osteoarthritis. Osteoarthritis Cartilage. 2002;10(4):277-81.
[92] Shen PC, Wu CL, Jou IM, Lee CH, Juan HY, Lee PJ, et al. T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein- 1gamma. Osteoarthritis Cartilage. 2011;19(6):728-36.
[93] Revell PA, Mayston V, Lalor P, Mapp P. The synovial membrane in osteoarthritis: a histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis. 1988;47(4):300-7.
[94] Xiang Y, Sekine T, Nakamura H, Imajoh-Ohmi S, Fukuda H, Nishioka K, et al. Proteomic surveillance of autoimmunity in osteoarthritis: identification oftriosephosphate isomerase as an autoantigen in patients with osteoarthritis. Arthritis Rheum. 2004;50(5):1511-21.
[95] Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr Opin Rheumatol. 2008;20(5):565-72.
[96] Chevalier X, Claudepierre P, Groult N, Zardi L, Hornebeck W. Presence of ED-A containing fibronectin in human articular cartilage from patients with osteoarthritis and rheumatoid arthritis. J Rheumatol. 1996;23(6):1022-30.
[97] Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB. NF-kappaB signaling: multiple angles to target OA. Curr Drug Targets. 2010;11(5):599-613.
[98] Chen LX, Lin L, Wang HJ, Wei XL, Fu X, Zhang JY, et al. Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-kappaBp65-specific siRNA. Osteoarthritis Cartilage. 2008;16(2):174-84.
[99] Khalife S, Zafarullah M. Molecular targets of natural health products in arthritis. Arthritis Res Ther. 2011;13(1):102.
[100] Tan C, Li L, Han J, Xu K, Liu X. A new strategy for osteoarthritis therapy: Inhibition of glycolysis. Front Pharmacol. 2022;13:1057229.
[101] Mobasheri A, Vannucci SJ, Bondy CA, Carter SD, Innes JF, Arteaga MF, et al. Glucose transport and metabolism in chondrocytes: a key to understanding chondrogenesis, skeletal development and cartilage degradation in osteoarthritis. Histol Histopathol. 2002;17(4):1239-67.
[102] Peansukmanee S, Vaughan-Thomas A, Carter SD, Clegg PD, Taylor S, Redmond C, et al. Effects of hypoxia on glucose transport in primary equine chondrocytes in vitro and evidence of reduced GLUT1 gene expression in pathologic cartilage in vivo. J Orthop Res. 2009;27(4):529-35.
[103] Rasheed Z, Akhtar N, Haqqi TM. Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end product-mediated activation of mitogen-activated protein kinases and nuclear factor-kappaB in human osteoarthritis chondrocytes. Rheumatology. 2011;50(5):838- 51.
[104] Bao C, Zhu S, Song K, He C. HK2: a potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways. Cell Commun Signal. 2022;20(1):132.
[105] Bustamante MF, Oliveira PG, Garcia-Carbonell R, Croft AP, Smith JM, Serrano RL, et al. Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis. Ann Rheum Dis. 2018;77(11):1636-43.
[106] Yang X, Chen W, Zhao X, Chen L, Li W, Ran J, et al. Pyruvate Kinase M2 Modulates the Glycolysis of Chondrocyte and Extracellular Matrix in Osteoarthritis. DNA Cell Biol. 2018;37(3):271-7.
[107] Qu J, Lu D, Guo H, Miao W, Wu G, Zhou M. PFKFB 3 modulates glycolytic metabolism and alleviates endoplasmic reticulum stress in human osteoarthritis cartilage. Clin Exp Pharmacol Physiol. 2016;43(3):312-8.
[108] Kaushik DK, Bhattacharya A, Mirzaei R, Rawji KS, Ahn Y, Rho JM, et al. Enhanced glycolytic metabolism supports transmigration of brain-infiltrating macrophages in multiple sclerosis. J Clin Invest. 2019;129(8):3277-92.
[109] Arra M, Swarnkar G, Ke K, Otero JE, Ying J, Duan X, et al. LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis. Nat Commun. 2020;11(1):3427.
[110] Alrushud AS, Rushton AB, Kanavaki AM, Greig CA. Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis. BMJ Open. 2017;7(6):e014537.
[111] Kulkarni K, Karssiens T, Kumar V, Pandit H. Obesity and osteoarthritis. Maturitas. 2016;89:22-8.
[112] Basu A, Schell J, Scofield RH. Dietary fruits and arthritis. Food Funct. 2018;9(1):70-7.
[113] Zhang J, Chen S, Wang C, Wang Y, Zhang Y, Du J. Rehabilitation effect of isokinetic muscle training combined with semiconductor laser on acute knee osteoarthritis. Int J Biomed Eng. 2019;6:216-21.
[114] Wang H, Ma B. Healthcare and Scientific Treatment of Knee Osteoarthritis. J Healthc Eng. 2022;2022:5919686.
[115] Dong R, Wu Y, Xu S, Zhang L, Ying J, Jin H, et al. Is aquatic exercise more effective than land-based exercise for knee osteoarthritis? Medicine. 2018;97(52).
[116] Kong LJ, Lauche R, Klose P, Bu JH, Yang XC, Guo CQ, et al. Tai Chi for Chronic Pain Conditions: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Sci Rep. 2016;6(1):25325.
[117] Li R, Sun J, Hu H, Zhang Q, Sun R, Zhou S, et al. Research Trends of Acupuncture Therapy on Knee Osteoarthritis from 2010 to 2019: A Bibliometric Analysis. J Pain Res. 2020;13:1901-13.
[118] Wu Y, Zhu S, Lv Z, Kan S, Wu Q, Song W, et al. Effects of therapeutic ultrasound for knee osteoarthritis: a systematic review and meta-analysis. Clin Rehabil. 2019;33(12):1863-75.
[119] Ahmad MA, MS AH, Yusof A. Effects of low-level and high-intensity laser therapy as adjunctive to rehabilitation exercise on pain, stiffness and function in knee osteoarthritis: a systematic review and meta-analysis. Physiotherapy. 2022;114:85- 95.
[120] Wu Q, Zhao J, Guo W. Efficacy of massage therapy in improving outcomes in knee osteoarthritis: A systematic review and meta-analysis. Complement Ther Clin Pract. 2022;46:101522.
[121] Gay C, Guiguet-Auclair C, Coste N, Boisseau N, Gerbaud L, Pereira B, et al. Limited effect of a self-management exercise program added to spa therapy for increasing physical activity in patients with knee osteoarthritis: A quasi-randomized controlled trial. Ann Phys Rehabil Med. 2020;63(3):181-8.
[122] Islam MU, Nayab M, Ansari AN. Effect of dry cupping versus soft and prolonged massage in the management of knee osteoarthritis - a randomized controlled clinical trial. J Complement Integr Med. 2021;18(4):797-804.
[123] Cheung C, Wyman JF, Peden-McAlpine C. Long-Term Yoga and Aerobic/Strength Exercise Adherence in Older Women with Knee Osteoarthritis: A Mixed Methods Approach. Int J Yoga Therap. 2022;32(2022):Article 4.
[124] Zhao Z, Wang R, Guo Y, Chen L, Wang K, Zhou H, et al. Static Low-Angle Squatting Reduces the Intra-Articular Inflammatory Cytokines and Improves the Performance of Patients with Knee Osteoarthritis. Biomed Res Int. 2019;2019:9617923.
[125] Zhao D, Chen Z, Hu S, Lin J, Shao Z, Wang G, et al. Efficacy and Safety of Loxoprofen Hydrogel Transdermal Patch Versus Loxoprofen Tablet in Chinese Patients with Myalgia: A Double-Blind, Double-Dummy, Parallel-Group, Randomized, Controlled, Non-Inferiority Trial. Clin Drug Investig. 2019;39(4):369-77.
[126] Coskun Benlidayi I, Gokcen N, Basaran S. Comparative short-term effectiveness of ibuprofen gel and cream phonophoresis in patients with knee osteoarthritis. Rheumatol Int. 2018;38(10):1927-32.
[127] Wadsworth LT, Kent JD, Holt RJ. Efficacy and safety of diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehiclecontrolled, 4 week study. Curr Med Res Opin. 2016;32(2):241-50.
[128] Luksurapan W, Boonhong J. Effects of phonophoresis of piroxicam and ultrasound on symptomatic knee osteoarthritis. Arch Phys Med Rehabil. 2013;94(2):250-5.
[129] Shabbir MA, Mehak F, Khan MR, Ahmed W, Nawaz MF, Hassoun A, et al. Unraveling the role of natural functional oils in modulating osteoarthritis related complications. Crit Rev Food Sci Nutr. 2023:1-21.
[130] Wei B, Zhang Y, Tang L, Ji Y, Yan C, Zhang X. Protective effects of quercetin against inflammation and oxidative stress in a rabbit model of knee osteoarthritis. Drug Dev Res. 2019;80(3):360-7.
[131] Ongchai S. Phyllanthus spp. as a Potential Alternative Treatment for Arthritic Conditions. Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases2019. p. 523-33.
[132] Bruyère O, Altman RD, Reginster J-Y, editors. Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: evidence from real-life setting trials and surveys. Semin Arthritis Rheum; 2016: Elsevier.
[133] Lomonte ABV, Mendonça JA, Brandão GdC, Castro ML. Multicenter, randomized, double-blind clinical trial to evaluate efficacy and safety of combined glucosamine sulfate and chondroitin sulfate capsules for treating knee osteoarthritis. Adv Rheumatol. 2019;58:41.
[134] Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J. 2015;15:1-15.
[135] Cooper C, Chapurlat R, Al-Daghri N, Herrero-Beaumont G, Bruyère O, Rannou F, et al. Safety of oral non-selective non-steroidal anti-inflammatory drugs in osteoarthritis: what does the literature say? Drugs Aging. 2019;36(Suppl 1):15-24.
[136] Pavelka K, Bruyere O, Cooper C, Kanis JA, Leeb BF, Maheu E, et al. Diacerein: Benefits, Risks and Place in the Management of Osteoarthritis. An Opinion-Based Report from the ESCEO. Drugs Aging. 2016;33(2):75-85.
[137] Lai JN, Chen HJ, Chen CC, Lin JH, Hwang JS, Wang JD. Duhuo jisheng tang for treating osteoarthritis of the knee: a prospective clinical observation. Chin Med. 2007;2:4.
[138] Saltychev M, Mattie R, McCormick Z, Laimi K. The Magnitude and Duration of the Effect of Intra-articular Corticosteroid Injections on Pain Severity in Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Am J Phys Med Rehabil. 2020;99(7):617-25.
[139] Kershen LM, Nacey NC, Patrie JT, Fox MG. Fluoroscopically Guided Facet Injections: Comparison of Intra-Articular and Periarticular Steroid and Anesthetic Injection on Immediate and Short-Term Pain Relief. AJNR Am J Neuroradiol. 2018;39(11):2161-5.
[140] Conaghan PG, Cohen SB, Berenbaum F, Lufkin J, Johnson JR, Bodick N. Brief report: a phase II b trial of a novel extendedrelease microsphere formulation of triamcinolone acetonide for intraarticular injection in knee osteoarthritis. Arthritis Rheumatol. 2018;70(2):204-11.
[141] Klocke R, Levasseur K, Kitas GD, Smith JP, Hirsch G. Cartilage turnover and intra-articular corticosteroid injections in knee osteoarthritis. Rheumatol Int. 2018;38(3):455-9.
[142] Feng X, Beiping L. Therapeutic Efficacy of Ozone Injection into the Knee for the Osteoarthritis Patient along with Oral Celecoxib and Glucosamine. J Clin Diagn Res. 2017;11(9):UC01-UC3.
[143] Emadedin M, Ghorbani Liastani M, Fazeli R, Mohseni F, Moghadasali R, Mardpour S, et al. Long-Term Follow-up of Intra-articular Injection of Autologous Mesenchymal Stem Cells in Patients with Knee, Ankle, or Hip Osteoarthritis. Arch Iran Med. 2015;18(6):336-44.
[144] Zhao B, Yu Y, Liu W, Du J. Efficacy of arthroscopic loose body removal for knee osteoarthritis. Exp Ther Med. 2018;15(2):1666-71.
[145] Hangody L, Kish G, Karpati Z, Udvarhelyi I, Szigeti I, Bely M. Mosaicplasty for the treatment of articular cartilage defects: application in clinical practice. Orthopedics. 1998;21(7):751-6.
[146] Gobbi A, Karnatzikos G, Kumar A. Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc. 2014;22(9):1986-96.
[147] Pannell WC, Heidari KS, Mayer EN, Zimmerman K, Heckmann N, McKnight B, et al. High Tibial Osteotomy Survivorship: A Population-Based Study. Orthop J Sports Med. 2019;7(12):2325967119890693.
[148] Qin D, Chen W, Wang J, Lv H, Ma W, Dong T, et al. Mechanism and influencing factors of proximal fibular osteotomy for treatment of medial compartment knee osteoarthritis: A prospective study. J Int Med Res. 2018;46(8):3114-23.
[149] Hoorntje A, van Ginneken BT, Kuijer P, Koenraadt KLM, van Geenen RCI, Kerkhoffs G, et al. Eight respectively nine out of ten patients return to sport and work after distal femoral osteotomy. Knee Surg Sports Traumatol Arthrosc. 2019;27(7):2345-53.
[150] Cao Z, Mai X, Wang J, Feng E, Huang Y. Unicompartmental Knee Arthroplasty vs High Tibial Osteotomy for Knee Osteoarthritis: A Systematic Review and Meta- Analysis. J Arthroplasty. 2018;33(3):952-9.
[151] Loures FB, Correia W, Reis JH, Pires EARS, de Paula Mozela A, de Souza EB, et al. Outcomes after knee arthroplasty in extra-articular deformity. Int Orthop. 2019;43(9):2065-70.
[152] Gregori D, Giacovelli G, Minto C, Barbetta B, Gualtieri F, Azzolina D, et al. Association of Pharmacological Treatments With Long-term Pain Control in Patients With KneeOsteoarthritis: A Systematic Review and Meta-analysis. JAMA. 2018;320(24):2564- 79.
[153] Shepard HM, Phillips GL, C DT, Feldmann M. Developments in therapy with monoclonal antibodies and related proteins. Clin Med (Lond). 2017;17(3):220-32.
[154] Das V, Kc R, Li X, I OS, van Wijnen AJ, Kroin JS, et al. Blockade of Vascular Endothelial Growth Factor Receptor-1 (Flt-1), Reveals a Novel Analgesic For Osteoarthritis- Induced Joint Pain. Gene Rep. 2018;11:94-100.
[155] Zheng S, Hunter DJ, Xu J, Ding C. Monoclonal antibodies for the treatment of osteoarthritis. Expert Opin Biol Ther. 2016;16(12):1529-40.
[156] Wang K, Xu J, Hunter DJ, Ding C. Investigational drugs for the treatment of osteoarthritis. Expert Opin Investig Drugs. 2015;24(12):1539-56.
[157] Werkmann D, Buyse MA, Dejager L, Cornelis S, Thudium CS, Karsdal MA, et al. In Vitro Characterization of the Adamts-5 Specific Nanobody® M6495. Osteoarthritis Cartilage. 2018;26:S178-S.
[158] Siebuhr AS, Werkmann D, Bay-Jensen AC, Thudium CS, Karsdal MA, Serruys B, et al. The Anti-ADAMTS-5 Nanobody((R)) M6495 Protects Cartilage Degradation Ex Vivo. Int J Mol Sci. 2020;21(17):5992.
[159] Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33-42.
[160] Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6(11):625-35.
[161] Tan Z, Chen R, Lin H, Wang H. The Identification of Immune-Related Biomarkers for Osteoarthritis Immunotherapy Based on Single-Cell RNA Sequencing Analysis. Genet Res (Camb). 2023;2023:5574636.
[162] Chen H, Tian Y. MiR-15a-5p regulates viability and matrix degradation of human osteoarthritis chondrocytes via targeting VEGFA. Biosci Trends. 2017;10(6):482-8.
[163] Xie W, Jiang L, Huang X, You W, Sun W. Hsa_circ_0004662 Accelerates the Progression of Osteoarthritis via the microRNA-424-5p/VEGFA Axis. Curr Mol Med. 2023.
[164] Ye S, Liu Q, Huang K, Jiang X, Zhang X. The comprehensive analysis based study of perfluorinated compounds-Environmental explanation of bladder cancer progression. Ecotoxicol Environ Saf. 2022;229:113059.
[165] Zhang X, Zhang TT, Ren XH, Chen XL, Wang SQ, Qin C. Pyrethroids Toxicity to Male Reproductive System and Offspring as a Function of Oxidative Stress Induction: Rodent Studies. Front Endocrinol (Lausanne). 2021;12:656106.
[166] Chiusaroli R, Visentini M, Galimberti C, Casseler C, Mennuni L, Covaceuszach S, et al. Targeting of ADAMTS5’s ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis. Osteoarthritis Cartilage. 2013;21(11):1807-10.
[167] Caselli G, Chiusaroli R, Visintin M, Piepoli T, Letari O, Grotti A, et al., editors. The Proteomic Profile of Histological Samples Derived from a Surgical Mouse Model of Osteoarthritis Reveals an Unexpected Mode of Action for the Anti-Aggrecanase- 2 Monoclonal Antibody CRB0017. ARTHRITIS & RHEUMATOLOGY; 2015: WILEYBLACKWELL 111 RIVER ST, HOBOKEN 07030-5774, NJ USA.
[168] Cohen SB, Proudman S, Kivitz AJ, Burch FX, Donohue JP, Burstein D, et al. A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. Arthritis Res Ther. 2011;13(4):R125.
[169] Chevalier X, Conrozier T, Richette P. Desperately looking for the right target in osteoarthritis: the anti-IL-1 strategy. Arthritis Res Ther. 2011;13(4):1-2.
[170] Fleischmann R, Bliddal H, Blanco F, Schnitzer T, Peterfy C, Chen S, et al. SAT0575 Safety and efficacy of lutikizumab (ABT-981), an anti–interleukin-1 alpha/beta dual variable domain (DVD) immunoglobulin, in subjects with knee osteoarthritis: results from the randomised, double-blind, placebo-controlled, parallel-group phase 2 trial. Ann Rheum Dis. 2018;77:1141-2.
[171] Kosloski MP, Goss S, Wang SX, Liu J, Loebbert R, Medema JK, et al. Pharmacokinetics and Tolerability of a Dual Variable Domain Immunoglobulin ABT-981 Against IL-1alpha and IL-1beta in Healthy Subjects and Patients With Osteoarthritis of the Knee. J Clin Pharmacol. 2016;56(12):1582-90.
[172] Cheleschi S, Cantarini L, Pascarelli NA, Collodel G, Lucherini OM, Galeazzi M, et al. Possible chondroprotective effect of canakinumab: an in vitro study on human osteoarthritic chondrocytes. Cytokine. 2015;71(2):165-72.
[173] Wang J. Efficacy and safety of adalimumab by intra-articular injection for moderate to severe knee osteoarthritis: An open-label randomized controlled trial. J Int Med Res. 2018;46(1):326-34.
[174] Güler-Yüksel M, Allaart C, Watt I, Goekoop-Ruiterman Y, de Vries-Bouwstra J, Van Schaardenburg D, et al. Treatment with TNF-α inhibitor infliximab might reduce hand osteoarthritis in patients with rheumatoid arthritis. Osteoarthritis Cartilage. 2010;18(10):1256-62.
[175] Zhang Q, Lv H, Chen A, Liu F, Wu X. Efficacy of infliximab in a rabbit model of osteoarthritis. Connect Tissue Res. 2012;53(5):355-8.
[176] Wang J, Zhao T, Tang S, Zhang S, Lv P, Li J, et al. Safety assessment of vitacoxib: 180-day chronic oral toxicity studies. Regul Toxicol Pharmacol. 2018;95:244-9.
[177] Mantyh PW, Koltzenburg M, Mendell LM, Tive L, Shelton DL. Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology. 2011;115(1):189- 204.
[178] Nagai T, Sato M, Kobayashi M, Yokoyama M, Tani Y, Mochida J. Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis. Arthritis Res Ther. 2014;16(5):427.
[179] Nijjar JS, Abbott-Banner K, Ray R, Vicente SM, Bentley J, Muya C, et al. Op0075 efficacy, safety, pharmacokinetics and immunogenicity of repeated dosing of gsk3858279 in patients with knee osteoarthritis: a phase i, randomized, doubleblind, placebo-controlled study. Ann Rheum Dis. 2023;82:51-2.
[180] Ma Y, Yang H, Zong X, Wu J, Ji X, Liu W, et al. Artificial M2 macrophages for diseasemodifying osteoarthritis therapeutics. Biomaterials. 2021;274:120865.
[181] Dai M, Sui B, Xue Y, Liu X, Sun J. Cartilage repair in degenerative osteoarthritis mediated by squid type II collagen via immunomodulating activation of M2 macrophages, inhibiting apoptosis and hypertrophy of chondrocytes. Biomaterials. 2018;180:91-103.
[182] Zhang HY, Lin CX, Zeng C, Wang ZY, Wang H, Lu JS, et al. Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2. Ann Rheum Dis. 2018;77(10):1524-34.
[183] Kraus VB, McDaniel G, Huebner JL, Stabler TV, Pieper CF, Shipes SW, et al. Direct in vivo evidence of activated macrophages in human osteoarthritis. Osteoarthritis Cartilage. 2016;24(9):1613-21.
[184] Zhang P, Dong B, Yuan P, Li X. Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review. J Orthop Surg Res. 2023;18(1):639.
[185] Wiggers TG, Winters M, Van den Boom NA, Haisma HJ, Moen MH. Autologous stem cell therapy in knee osteoarthritis: a systematic review of randomised controlled trials. Br J Sports Med. 2021;55(20):1161-9.
[186] Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol. 2009;217(2):318-24.
[187] Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076-84.
[188] D’Arrigo D, Roffi A, Cucchiarini M, Moretti M, Candrian C, Filardo G. Secretome and extracellular vesicles as new biological therapies for knee osteoarthritis: a systematic review. J Clin Med. 2019;8(11):1867.
[189] Desando G, Cavallo C, Sartoni F, Martini L, Parrilli A, Veronesi F, et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther. 2013;15(1):R22.
[190] Mei L, Shen B, Ling P, Liu S, Xue J, Liu F, et al. Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model. PLoS One. 2017;12(4):e0176107.
[191] Perdisa F, Gostynska N, Roffi A, Filardo G, Marcacci M, Kon E. Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence. Stem Cells Int. 2015;2015:597652.
[192] Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14(3):213-30.
[193] Filardo G, Tschon M, Perdisa F, Brogini S, Cavallo C, Desando G, et al. Microfragmentation is a valid alternative to cell expansion and enzymatic digestion of adipose tissue for the treatment of knee osteoarthritis: a comparative preclinical study. Knee Surg Sports Traumatol Arthrosc. 2022;30(3):773-81.
[194] Tantuway V, Thomas W, Parikh MB, Sharma R, Jeyaraman N, Jeyaraman M. Clinical Outcome of Minimally Manipulated, Mechanically Isolated Autologous Adipose Tissue-Derived Stromal Vascular Fraction (Sahaj Therapy(R)) in Knee Osteoarthritis- Randomized Controlled Trial. Indian J Orthop. 2023;57(10):1646-58.
[195] Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Lopez- Elio S, et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2018;16(1):213.
[196] Jeyaraman M, Muthu S, Jeyaraman N, Ranjan R, Jha SK, Mishra P. Synovium Derived Mesenchymal Stromal Cells (Sy-MSCs): A Promising Therapeutic Paradigm in the Management of Knee Osteoarthritis. Indian J Orthop. 2022;56(1):1-15.
[197] Kim GB, Shon OJ. Current perspectives in stem cell therapies for osteoarthritis of the knee. Yeungnam Univ J Med. 2020;37(3):149-58.
[198] Dhillon J, Kraeutler MJ, Belk JW, Scillia AJ. Umbilical Cord-Derived Stem Cells for the Treatment of Knee Osteoarthritis: A Systematic Review. Orthop J Sports Med. 2022;10(7):23259671221104409.
[199] Zhang M, Hu W, Cai C, Wu Y, Li J, Dong S. Advanced application of stimuliresponsive drug delivery system for inflammatory arthritis treatment. Mater Today Bio. 2022;14:100223.
[200] Lu J, Zhang Y, Yang X, Zhao H. Harnessing exosomes as cutting-edge drug delivery systems for revolutionary osteoarthritis therapy. Biomed Pharmacother. 2023;165:115135.
[201] Fan WJ, Liu D, Pan LY, Wang WY, Ding YL, Zhang YY, et al. Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment. Front Cell Dev Biol. 2022;10:949690.
[202] Zhang Y, Wang X, Chen J, Qian D, Gao P, Qin T, et al. Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis. J Nanobiotechnology. 2022;20(1):56.
[203] Qiu B, Xu X, Yi P, Hao Y. Curcumin reinforces MSC-derived exosomes in attenuating osteoarthritis via modulating the miR-124/NF-kB and miR-143/ROCK1/TLR9 signalling pathways. J Cell Mol Med. 2020;24(18):10855-65.
[204] Sun W, Qu S, Ji M, Sun Y, Hu B. BMP-7 modified exosomes derived from synovial mesenchymal stem cells attenuate osteoarthritis by M2 polarization of macrophages. Heliyon. 2023;9(9):e19934.
[205] Estebanez B, Jimenez-Pavon D, Huang CJ, Cuevas MJ, Gonzalez-Gallego J. Effects of exercise on exosome release and cargo in in vivo and ex vivo models: A systematic review. J Cell Physiol. 2021;236(5):3336-53.
[206] Huang Y, Zhang X, Zhan J, Yan Z, Chen D, Xue X, et al. Bone marrow mesenchymal stem cell-derived exosomal miR-206 promotes osteoblast proliferation and differentiation in osteoarthritis by reducing Elf3. J Cell Mol Med. 2021;25(16):7734-45.
[207] Xu C, Mi Z, Dong Z, Chen X, Ji G, Kang H, et al. Platelet-Derived Exosomes Alleviate Knee Osteoarthritis by Attenuating Cartilage Degeneration and Subchondral Bone Loss. Am J Sports Med. 2023;51(11):2975-85.
[208] Jin Y, Xu M, Zhu H, Dong C, Ji J, Liu Y, et al. Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis. J Cell Mol Med. 2021;25(19):9281-94.
[209] Zhou QF, Cai YZ, Lin XJ. The dual character of exosomes in osteoarthritis: Antagonists and therapeutic agents. Acta Biomater. 2020;105:15-25.
[210] Guillen MI, Tofino-Vian M, Silvestre A, Castejon MA, Alcaraz MJ. Role of peroxiredoxin 6 in the chondroprotective effects of microvesicles from human adipose tissue-derived mesenchymal stem cells. J Orthop Translat. 2021;30:61-9.
[211] Li P, Lv S, Jiang W, Si L, Liao B, Zhao G, et al. Exosomes derived from umbilical cord mesenchymal stem cells protect cartilage and regulate the polarization of macrophages in osteoarthritis. Ann Transl Med. 2022;10(18):976.
[212] Madry H, Cucchiarini M. Gene therapy for human osteoarthritis: principles and clinical translation. Expert Opin Biol Ther. 2016;16(3):331-46.
[213] Karlsen TA, de Souza GA, Odegaard B, Engebretsen L, Brinchmann JE. microRNA- 140 Inhibits Inflammation and Stimulates Chondrogenesis in a Model of Interleukin 1beta-induced Osteoarthritis. Mol Ther Nucleic Acids. 2016;5(10):e373.
[214] Nakamura A, Rampersaud YR, Sharma A, Lewis SJ, Wu B, Datta P, et al. Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. JCI Insight. 2016;1(12).
[215] Wijesinghe SN, Lindsay MA, Jones SW. Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review. Biomedicines. 2021;9(8):902.
[216] Evans CH, Ghivizzani SC, Robbins PD. Osteoarthritis gene therapy in 2022. Curr Opin Rheumatol. 2023;35(1):37-43.
[217] Tao SC, Yuan T, Rui BY, Zhu ZZ, Guo SC, Zhang CQ. Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway. Theranostics. 2017;7(3):733-50.
[218] Fang Z, Yang X, Wu G, Liu M, Han J, Tao K, et al. The use of autologous plateletrich plasma gel increases wound healing and reduces scar development in splitthickness skin graft donor sites. J Plast Surg Hand Surg. 2019;53(6):356-60.
[219] Valentini CG, Nuzzolo ER, Bianchi M, Orlando N, Iachininoto MG, Pinci P, et al. Cord Blood Platelet Lysate: In Vitro Evaluation to Support the Use in Regenerative Medicine. Mediterr J Hematol Infect Dis. 2019;11(1):e2019021.
[220] Jafarpour M, Omidvar MH, Soltani-Zangbar MS, Dolati S, Ahmadi M, Jadidi-Niaragh F, et al. The effects of PBMCs-derived exosomes of ankylosing spondylitis patients on T cell profiles. Gene Reports. 2022;26:101446.
[221] Hosseini S, Soltani-Zangbar MS, Zamani M, Yaghoubi Y, Rikhtegar Ghiasi R, Motavalli R, et al. Comparative evaluation of autologous platelet-rich plasma and platelet lysate in patients with knee osteoarthritis. Growth Factors. 2023;41(3):165-77.
[222] Bennell KL, Hunter DJ, Paterson KL. Platelet-Rich Plasma for the Management of Hip and Knee Osteoarthritis. Curr Rheumatol Rep. 2017;19(5):24.
[223] Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016;45(4 Suppl):S28-33.
[224] Airenne KJ, Hu YC, Kost TA, Smith RH, Kotin RM, Ono C, et al. Baculovirus: an insectderived vector for diverse gene transfer applications. Mol Ther. 2013;21(4):739-49.
[225] Kim YS, Guilak F. Engineering Hyaluronic Acid for the Development of New Treatment Strategies for Osteoarthritis. Int J Mol Sci. 2022;23(15):8662.
[226] Moreland LW. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. Arthritis Res Ther. 2003;5(2):54-67.
[227] Yazici Y, McAlindon TE, Fleischmann R, Gibofsky A, Lane NE, Kivitz AJ, et al. A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study. Osteoarthritis Cartilage. 2017;25(10):1598-606.
[228] Childs BG, Gluscevic M, Baker DJ, Laberge RM, Marquess D, Dananberg J, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017;16(10):718-35.
[229] Jeon OH, Kim C, Laberge RM, Demaria M, Rathod S, Vasserot AP, et al. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat Med. 2017;23(6):775- 81.
[230] van Deursen JM. Senolytic therapies for healthy longevity. Science. 2019;364(6441):636-7.
[231] Atobe M. Activation of Transient Receptor Potential Vanilloid (TRPV) 4 as a Therapeutic Strategy in Osteoarthritis. Curr Top Med Chem. 2019;19(24):2254-67.
[232] Li CS, Zheng Z, Ha P, Jiang WL, Berthiaume EA, Lee S, et al. Neural EGFL like 1 as a potential pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug. Biomaterials. 2020;226:119541.
[233] Kjelgaard-Petersen CF, Sharma N, Kayed A, Karsdal MA, Mobasheri A, Hagglund P, et al. Tofacitinib and TPCA-1 exert chondroprotective effects on extracellular matrix turnover in bovine articular cartilage ex vivo. Biochem Pharmacol. 2019;165:91-8.
[234] Yazici Y, McAlindon TE, Gibofsky A, Lane NE, Lattermann C, Skrepnik N, et al. A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis. Osteoarthritis Cartilage. 2021;29(5):654-66.
[235] Guo H, Yin W, Zou Z, Zhang C, Sun M, Min L, et al. Quercitrin alleviates cartilage extracellular matrix degradation and delays ACLT rat osteoarthritis development: An in vivo and in vitro study. J Adv Res. 2021;28:255-67.
[236] Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol. 2014;10(1):11-22.
[237] Colella F, Garcia JP, Sorbona M, Lolli A, Antunes B, D’Atri D, et al. Drug delivery in intervertebral disc degeneration and osteoarthritis: Selecting the optimal platform for the delivery of disease-modifying agents. J Control Release. 2020;328:985-99.
[238] Elron-Gross I, Glucksam Y, Margalit R. Liposomal dexamethasone-diclofenac combinations for local osteoarthritis treatment. Int J Pharm. 2009;376(1-2):84-91.
[239] Kang ML, Jeong SY, Im GI. Hyaluronic Acid Hydrogel Functionalized with Self- Assembled Micelles of Amphiphilic PEGylated Kartogenin for the Treatment of Osteoarthritis. Tissue Eng Part A. 2017;23(13-14):630-639.
[240] Elron-Gross I, Glucksam Y, Melikhov D, Margalit R. Cyclooxygenase inhibition by diclofenac formulated in bioadhesive carriers. Biochim Biophys Acta. 2008;1778(4):931-6.
[241] Lu HT, Sheu MT, Lin YF, Lan J, Chin YP, Hsieh MS, et al. Injectable hyaluronic-aciddoxycycline hydrogel therapy in experimental rabbit osteoarthritis. BMC Vet Res. 2013;9:68.
[242] Sandker MJ, Petit A, Redout EM, Siebelt M, Muller B, Bruin P, et al. In situ forming acyl-capped PCLA-PEG-PCLA triblock copolymer based hydrogels. Biomaterials. 2013;34(32):8002-8011.
[243] Lolli A, Sivasubramaniyan K, Vainieri ML, Oieni J, Kops N, Yayon A, et al. Hydrogelbased delivery of antimiR-221 enhances cartilage regeneration by endogenous cells. J Control Release. 2019;309:220-230.
[244] Chahla J, Mannava S, Cinque ME, Geeslin AG, Codina D, LaPrade RF. Bone Marrow Aspirate Concentrate Harvesting and Processing Technique. Arthrosc Tech. 2017;6(2):e441-e5.
[245] Lin J, Scheinberg M. BMAC Injection Improves 65-Year Old’s Knee Osteoarthritis Pain. Stem Cells Regen Med. 2023;7(1):1-2.
[246] Yu LK, Zhang J, Sun ZY, Ruan CL, Li H, Ruan XJ. Coculture with interleukin-10 overexpressed chondrocytes: A cell therapy model to ameliorate the post-traumatic osteoarthritis development. J Biol Regul Homeost Agents. 2021;35(2):593-603.