Role of Apoptosis in the Pathogenesis of Osteoarthritis: An Explicative
Review

Deepshi      Arora; Yugam      Taneja; Anjali      Sharma; Ashwani      Dhingra; Kumar      Guarve

doi:10.2174/1573397119666230904150741

Abstract

Apoptosis is a complex regulatory, active cell death process that plays a role in cell development, homeostasis, and ageing. Cancer, developmental defects, and degenerative diseases are all pathogenic disorders caused by apoptosis dysregulation. Osteoarthritis (OA) is by far the most frequently diagnosed joint disease in the aged, and it is characterized by the ongoing breakdown of articular cartilage, which causes severe disability. Multiple variables regulate the anabolic and catabolic pathways of the cartilage matrix, which either directly or indirectly contribute to cartilage degeneration in osteoarthritis. Articular cartilage is a highly specialized tissue made up of an extracellular matrix of cells that are tightly packed together. As a result, chondrocyte survival is crucial for the preservation of an optimal cartilage matrix, and chondrocyte characteristics and survival compromise may result in articular cartilage failure. Inflammatory cytokines can either promote or inhibit apoptosis, the process of programmed cell death. Pro-apoptotic cytokines like TNF-α can induce cell death, while anti-apoptotic cytokines like IL-4 and IL-10 protect against apoptosis. The balance between these cytokines plays a critical role in determining cell fate and has implications for tissue damage and disease progression. Similarly, they contribute to the progression of OA by disrupting the metabolic balance in joint tissues by promoting catabolic and anabolic pathways. Their impact on cell joints, as well as the impacts of cell signalling pathways on cytokines and inflammatory substances, determines their function in osteoarthritis development. Apoptosis is evident in osteoarthritic cartilage; however, determining the relative role of chondrocyte apoptosis in the aetiology of OA is difficult, and the rate of apoptotic chondrocytes in osteoarthritic cartilage is inconsistent. The current study summarises the role of apoptosis in the development of osteoarthritis, the mediators, and signalling pathways that trigger the cascade of events, and the other inflammatory features involved.

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Graphical Abstract

[1]
Kestilä I, Thevenot J, Finnilä MA, et al. In vitro method for 3D morphometry of human articular cartilage chondrons based on micro-computed tomography. Osteoarthritis Cartilage  2018; 26(8): 1118-26.
 [http://dx.doi.org/10.1016/j.joca.2018.05.012] [PMID: 29802974]

[2]
Hall AC. The role of chondrocyte morphology and volume in controlling phenotype—implications for osteoarthritis, cartilage repair, and cartilage engineering. Curr Rheumatol Rep  2019; 21(8): 38.
 [http://dx.doi.org/10.1007/s11926-019-0837-6] [PMID: 31203465]

[3]
Lotz M, Loeser RF. Effects of aging on articular cartilage homeostasis. Bone  2012; 51(2): 241-8.
 [http://dx.doi.org/10.1016/j.bone.2012.03.023] [PMID: 22487298]

[4]
Prasadam I, Farnaghi S, Feng JQ, et al. Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes: Role of integrinβ1 and focal adhesion kinase signaling cues. Arthritis Res Ther  2013; 15(5): R150.
 [http://dx.doi.org/10.1186/ar4333] [PMID: 24289792]

[5]
Tatari H. The structure, physiology, and biomechanics of articular cartilage: Injury and repair. Acta Orthop Traumatol Turc  2007; 41(S2): 1-5.
 [PMID: 18180577]

[6]
Kühn K, Shikhman AR, Lotz M. Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis. J Cell Physiol  2003; 197(3): 379-87.
 [http://dx.doi.org/10.1002/jcp.10372] [PMID: 14566967]

[7]
Sherwood JC, Bertrand J, Eldridge SE, Dell’Accio F. Cellular and molecular mechanisms of cartilage damage and repair. Drug Discov Today  2014; 19(8): 1172-7.
 [http://dx.doi.org/10.1016/j.drudis.2014.05.014] [PMID: 24880104]

[8]
Ribe EM, Serrano-Saiz E, Akpan N, Troy CM. Mechanisms of neuronal death in disease: Defining the models and the players. Biochem J  2008; 415(2): 165-82.
 [http://dx.doi.org/10.1042/BJ20081118] [PMID: 18800967]

[9]
D’Arcy MS. Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int  2019; 43(6): 582-92.
 [http://dx.doi.org/10.1002/cbin.11137] [PMID: 30958602]

[10]
Fahmi T, Wang X, Zhdanov DD, et al. DNase I induces other endonucleases in kidney tubular epithelial cells by Its DNA-degrading activity. Int J Mol Sci  2020; 21(22): 8665.

[11]
Goggs R, Carter SD, Schulze-Tanzil G, Shakibaei M, Mobasheri A. Apoptosis and the loss of chondrocyte survival signals contribute to articular cartilage degradation in osteoarthritis. Vet J  2003; 166(2): 140-58.
 [http://dx.doi.org/10.1016/S1090-0233(02)00331-3] [PMID: 12902179]

[12]
Liu C, Zhang K, Shen H, Yao X, Sun Q, Chen G. Necroptosis: A novel manner of cell death, associated with stroke (Review). Int J Mol Med  2018; 41(2): 624-30.
 [PMID: 29207014]

[13]
Nasimian A, Farzaneh P, Tamanoi F, Bathaie SZ. Cytosolic and mitochondrial ROS production resulted in apoptosis induction in breast cancer cells treated with Crocin: The role of FOXO3a, PTEN and AKT signaling. Biochem Pharmacol  2020; 177: 113999.
 [http://dx.doi.org/10.1016/j.bcp.2020.113999] [PMID: 32353423]

[14]
Wang A, Liu J, Yang Y, et al. Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells. Chin Med  2021; 16(1): 16.
 [PMID: 33526051]

[15]
Kua VM, Kean NW, Sreenivasan S, Lai NS. Opioids in inducing cell apoptosis: A mini review. JBCS  2017; 24(1): 53-61.

[16]
Majtnerová P, Roušar T. An overview of apoptosis assays detecting DNA fragmentation. Mol Biol Rep  2018; 45(5): 1469-78.
 [http://dx.doi.org/10.1007/s11033-018-4258-9] [PMID: 30022463]

[17]
Kiadaliri AA, Lohmander LS, Moradi-Lakeh M, Petersson IF, Englund M. High and rising burden of hip and knee osteoarthritis in the Nordic region, 1990–2015: Findings from the Global Burden of Disease Study 2015. Acta Orthop  2015; 89(2): 177-83.

[18]
Palazzo C, Nguyen C, Lefevre-Colau MM, Rannou F, Poiraudeau S. Risk factors and burden of osteoarthritis. Ann Phys Rehabil Med  2016; 59(3): 134-8.
 [http://dx.doi.org/10.1016/j.rehab.2016.01.006] [PMID: 26904959]

[19]
Sandell LJ. Etiology of osteoarthritis: Genetics and synovial joint development. Nat Rev Rheumatol  2012; 8(2): 77-89.
 [http://dx.doi.org/10.1038/nrrheum.2011.199] [PMID: 22231237]

[20]
Young BL, Watson SL, Perez JL, McGwin G, Singh JA, Ponce BA. Trends in joint replacement surgery in patients with rheumatoid arthritis. J Rheumatol  2018; 45(2): 158-64.
 [http://dx.doi.org/10.3899/jrheum.170001] [PMID: 29196384]

[21]
Kim H, Blanco F. Cell death and apoptosis in osteoarthritic cartilage. Curr Drug Targets  2007; 8(2): 333-45.
 [http://dx.doi.org/10.2174/138945007779940025] [PMID: 17305511]

[22]
Zhang M, Mani SB, He Y, et al. Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis. J Clin Invest  2016; 126(8): 2893-902.
 [http://dx.doi.org/10.1172/JCI83676] [PMID: 27427985]

[23]
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: A disease of the joint as an organ. Arthritis Rheum  2012; 64(6): 1697-707.
 [http://dx.doi.org/10.1002/art.34453] [PMID: 22392533]

[24]
Zlatković J, Filipović D. Bax and B-cell-lymphoma 2 mediate proapoptotic signaling following chronic isolation stress in rat brain. Neuroscience  2012; 223: 238-45.
 [http://dx.doi.org/10.1016/j.neuroscience.2012.08.005] [PMID: 22885231]

[25]
Gartner A, Boag PR, Blackwell TK. Germline survival and apoptosis. WormBook: The Online Review of C elegans Biology.  2018.

[26]
Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol  2019; 20(3): 175-93.
 [http://dx.doi.org/10.1038/s41580-018-0089-8] [PMID: 30655609]

[27]
Gross A, Katz SG. Non-apoptotic functions of BCL-2 family proteins. Cell Death Differ  2017; 24(8): 1348-58.
 [http://dx.doi.org/10.1038/cdd.2017.22] [PMID: 28234359]

[28]
Siddiqui WA, Ahad A, Ahsan H. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch Toxicol  2015; 89(3): 289-317.
 [http://dx.doi.org/10.1007/s00204-014-1448-7] [PMID: 25618543]

[29]
Glab JA, Cao Z, Puthalakath H. Bcl-2 family proteins, beyond the veil. Int Rev Cell Mol Biol  2020; 351: 1-22.
 [http://dx.doi.org/10.1016/bs.ircmb.2019.12.001] [PMID: 32247577]

[30]
Glyn-Jones S, Palmer AJR, Agricola R, et al. Osteoarthritis. Lancet  2015; 386(9991): 376-87.
 [http://dx.doi.org/10.1016/S0140-6736(14)60802-3] [PMID: 25748615]

[31]
Yang HY, Liu YZ, Zhou XD, Huang Y, Xu NW. Role of IL-17 gene polymorphisms in osteoarthritis: A meta-analysis based on observational studies. World J Clin Cases  2020; 8(11): 2280-93.
 [http://dx.doi.org/10.12998/wjcc.v8.i11.2280] [PMID: 32548158]

[32]
Komori T. Functions of the osteocyte network in the regulation of bone mass. Cell Tissue Res  2013; 352(2): 191-8.
 [http://dx.doi.org/10.1007/s00441-012-1546-x] [PMID: 23329124]

[33]
Ramírez JP, Bonati-Richardson F, García MP, et al. Intra-articular treatment with corticosteroids increases apoptosis in human rotator cuff tears. Connect Tissue Res  2019; 60(3): 283-90.
 [http://dx.doi.org/10.1080/03008207.2018.1501040] [PMID: 30091643]

[34]
Hosseinzadeh A, Kamrava SK, Joghataei MT, et al. Apoptosis signaling pathways in osteoarthritis and possible protective role of melatonin. J Pineal Res  2016; 61(4): 411-25.
 [http://dx.doi.org/10.1111/jpi.12362] [PMID: 27555371]

[35]
Cabahug-Zuckerman P, Frikha-Benayed D, Majeska RJ, et al. Osteocyte apoptosis caused by hindlimb unloading is required to trigger osteocyte RANKL production and subsequent resorption of cortical and trabecular bone in mice femurs. J Bone Miner Res  2016; 31(7): 1356-65.
 [http://dx.doi.org/10.1002/jbmr.2807] [PMID: 26852281]

[36]
Pouresmaeili F, Kamali Dehghan B, Kamarehei M, Yong Meng G. A comprehensive overview on osteoporosis and its risk factors. Ther Clin Risk Manag  2018; 14: 2029-49.
 [http://dx.doi.org/10.2147/TCRM.S138000] [PMID: 30464484]

[37]
Huang T, Wang J, Zhou Y, Zhao Y, Hang D, Cao Y. LncRNA CASC2 is up-regulated in osteoarthritis and participates in the regulation of IL-17 expression and chondrocyte proliferation and apoptosis. Biosci Rep  2019; 39(5): BSR20182454.
 [http://dx.doi.org/10.1042/BSR20182454] [PMID: 31015370]

[38]
Li P, Xue WJ, Feng Y, Mao QS. Long non-coding RNA CASC2 suppresses the proliferation of gastric cancer cells by regulating the MAPK signaling pathway. Am J Transl Res  2016; 8(8): 3522-9.
 [PMID: 27648142]

[39]
Huang Z, Stabler T, Pei F, Kraus V. Both systemic and local lipopolysaccharide (LPS) burden is associated with knee osteoarthritis (OA). Osteoarthr Cartil  2016; 24: S329-30.
 [http://dx.doi.org/10.1016/j.joca.2016.01.590]

[40]
Obeng E. Apoptosis (programmed cell death) and its signals - A review. Braz J Biol  2021; 81(4): 1133-43.
 [http://dx.doi.org/10.1590/1519-6984.228437] [PMID: 33111928]

[41]
Shi J, Zhao Y, Wang Y, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature  2014; 514(7521): 187-92.
 [http://dx.doi.org/10.1038/nature13683] [PMID: 25119034]

[42]
Julien O, Wells JA. Caspases and their substrates. Cell Death Differ  2017; 24(8): 1380-9.
 [http://dx.doi.org/10.1038/cdd.2017.44] [PMID: 28498362]

[43]
Dhani S, Zhao Y, Zhivotovsky B. A long way to go: Caspase inhibitors in clinical use. Cell Death Dis  2021; 12(10): 949.
 [http://dx.doi.org/10.1038/s41419-021-04240-3] [PMID: 34654807]

[44]
García de la Cadena S, Massieu L. Caspases and their role in inflammation and ischemic neuronal death. Focus on caspase-12. Apoptosis  2016; 21(7): 763-77.
 [http://dx.doi.org/10.1007/s10495-016-1247-0] [PMID: 27142195]

[45]
Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol  2020; 21(2): 85-100.
 [http://dx.doi.org/10.1038/s41580-019-0173-8] [PMID: 31636403]

[46]
Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ  2006; 13(8): 1351-9.
 [http://dx.doi.org/10.1038/sj.cdd.4401987] [PMID: 16763616]

[47]
Vervliet T, Parys JB, Bultynck G. Bcl-2 proteins and calcium signaling: Complexity beneath the surface. Oncogene  2016; 35(39): 5079-92.
 [http://dx.doi.org/10.1038/onc.2016.31] [PMID: 26973249]

[48]
Delaunay-Moisan A, Appenzeller-Herzog C. The antioxidant machinery of the endoplasmic reticulum: Protection and signaling. Free Radic Biol Med  2015; 83: 341-51.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.019] [PMID: 25744411]

[49]
Roux S, Lambert-Comeau P, Saint-Pierre C, Lépine M, Sawan B, Parent JL. Death receptors, Fas and TRAIL receptors, are involved in human osteoclast apoptosis. Biochem Biophys Res Commun  2005; 333(1): 42-50.
 [http://dx.doi.org/10.1016/j.bbrc.2005.05.092] [PMID: 15936719]

[50]
Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci  2001; 26(1): 61-6.
 [http://dx.doi.org/10.1016/S0968-0004(00)01740-0] [PMID: 11165519]

[51]
Goldberg M, Nadiv O, Luknar-Gabor N, Agar G, Beer Y, Katz Y. Synergism between tumor necrosis factor alpha and interleukin-17 to induce IL-23 p19 expression in fibroblast-like synoviocytes. Mol Immunol  2009; 46(8-9): 1854-9.
 [http://dx.doi.org/10.1016/j.molimm.2009.01.004] [PMID: 19201028]

[52]
Hardy RS, Hülso C, Liu Y, et al. Characterisation of fibroblast-like synoviocytes from a murine model of joint inflammation. Arthritis Res Ther  2013; 15(1): R24.
 [http://dx.doi.org/10.1186/ar4158] [PMID: 23363614]

[53]
Thomas CM, Whittles CE, Fuller CJ, Sharif M. Variations in chondrocyte apoptosis may explain the increased prevalence of osteoarthritis in some joints. Rheumatol Int  2011; 31(10): 1341-8.
 [http://dx.doi.org/10.1007/s00296-010-1471-9] [PMID: 20396889]

[54]
Dinarello CA, Simon A, van der Meer JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov  2012; 11(8): 633-52.
 [http://dx.doi.org/10.1038/nrd3800] [PMID: 22850787]

[55]
Tang QO, Shakib K, Heliotis M, et al. TGF-β3: A potential biological therapy for enhancing chondrogenesis. Expert Opin Biol Ther  2009; 9(6): 689-701.
 [http://dx.doi.org/10.1517/14712590902936823] [PMID: 19426117]

[56]
Kaczanowski S. Apoptosis: Its origin, history, maintenance and the medical implications for cancer and aging. Phys Biol  2016; 13(3): 031001.
 [http://dx.doi.org/10.1088/1478-3975/13/3/031001] [PMID: 27172135]

[57]
Nguyen C, Pandey S. Exploiting mitochondrial vulnerabilities to trigger apoptosis selectively in cancer cells. Cancers  2019; 11(7): 916.
 [http://dx.doi.org/10.3390/cancers11070916] [PMID: 31261935]

[58]
Andersen MB, Pingel J, Kjær M, Langberg H. Interleukin-6: A growth factor stimulating collagen synthesis in human tendon. J Appl Physiol  2011; 110(6): 1549-54.
 [http://dx.doi.org/10.1152/japplphysiol.00037.2010] [PMID: 21350025]

[59]
Van Herreweghe F, Festjens N, Declercq W, Vandenabeele P. Tumor necrosis factor-mediated cell death: to break or to burst, that’s the question. Cell Mol Life Sci  2010; 67(10): 1567-79.
 [http://dx.doi.org/10.1007/s00018-010-0283-0] [PMID: 20198502]

[60]
Kaufmann T, Strasser A, Jost PJ. Fas death receptor signalling: Roles of Bid and XIAP. Cell Death Differ  2012; 19(1): 42-50.
 [http://dx.doi.org/10.1038/cdd.2011.121] [PMID: 21959933]

[61]
Verbruggen G, Wittoek R, Cruyssen BV, Elewaut D. Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: A double blind, randomised trial on structure modification. Ann Rheum Dis  2012; 71(6): 891-8.
 [http://dx.doi.org/10.1136/ard.2011.149849] [PMID: 22128078]

[62]
Chen B, Deng Y, Tan Y, Qin J, Chen LB. Association between severity of knee osteoarthritis and serum and synovial fluid interleukin 17 concentrations. J Int Med Res  2014; 42(1): 138-44.
 [http://dx.doi.org/10.1177/0300060513501751] [PMID: 24319050]

[63]
Varela-Eirin M, Loureiro J, Fonseca E, et al. Cartilage regeneration and ageing: Targeting cellular plasticity in osteoarthritis. Ageing Res Rev  2018; 42: 56-71.
 [http://dx.doi.org/10.1016/j.arr.2017.12.006] [PMID: 29258883]

[64]
Messina OD, Vidal Wilman M, Vidal Neira LF. Nutrition, osteoarthritis and cartilage metabolism. Aging Clin Exp Res  2019; 31(6): 807-13.
 [http://dx.doi.org/10.1007/s40520-019-01191-w] [PMID: 30982220]

[65]
Primorac D, Molnar V, Matišić V, et al. Comprehensive review of knee osteoarthritis pharmacological treatment and the latest professional societies’ guidelines. Pharmaceuticals  2021; 14(3): 205.
 [http://dx.doi.org/10.3390/ph14030205] [PMID: 33801304]

[66]
Massicotte F, Lajeunesse D, Benderdour M, et al. Can altered production of interleukin-1β, interleukin-6, transforming growth factor-β and prostaglandin E2 by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients. Osteoarthritis Cartilage  2002; 10(6): 491-500.
 [http://dx.doi.org/10.1053/joca.2002.0528] [PMID: 12056853]

[67]
Mehta AK, Gracias DT, Croft M. TNF activity and T cells. Cytokine  2018; 101: 14-8.
 [http://dx.doi.org/10.1016/j.cyto.2016.08.003] [PMID: 27531077]

[68]
Tang P, Hung M-C, Klostergaard J. Human pro-tumor necrosis factor is a homotrimer. Biochemistry  1996; 35(25): 8216-25.
 [http://dx.doi.org/10.1021/bi952182t] [PMID: 8679576]

[69]
Fu Q, Fu TM, Cruz AC, et al. Structural basis and functional role of intramembrane trimerization of the Fas/CD95 death receptor. Mol Cell  2016; 61(4): 602-13.
 [http://dx.doi.org/10.1016/j.molcel.2016.01.009] [PMID: 26853147]

[70]
Robinson WH, Lepus CM, Wang Q, et al. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol  2016; 12(10): 580-92.
 [http://dx.doi.org/10.1038/nrrheum.2016.136] [PMID: 27539668]

[71]
Ruan G, Xu J, Wang K, et al. Associations between serum IL-8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis. Clin Rheumatol  2019; 38(12): 3609-17.
 [http://dx.doi.org/10.1007/s10067-019-04718-8] [PMID: 31377918]

[72]
Tsuchida AI, Beekhuizen M, ’t Hart MC, et al. Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes. Arthritis Res Ther  2014; 16(5): 441.
 [http://dx.doi.org/10.1186/s13075-014-0441-0] [PMID: 25256035]

[73]
Koh SM, Chan CK, Teo SH, et al. Elevated plasma and synovial fluid interleukin-8 and interleukin-18 may be associated with the pathogenesis of knee osteoarthritis. Knee  2020; 27(1): 26-35.
 [http://dx.doi.org/10.1016/j.knee.2019.10.028] [PMID: 31917106]

[74]
Takahashi A, de Andrés MC, Hashimoto K, Itoi E, Oreffo ROC. Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthr Cartil  2015; 23(11): 1946-54.
 [http://dx.doi.org/10.1016/j.joca.2015.02.168] [PMID: 26521741]

[75]
Na HS, Park JS, Cho KH, et al. Interleukin-1-interleukin-17 signaling axis induces cartilage destruction and promotes experimental osteoarthritis. Front Immunol  2020; 11: 730.
 [http://dx.doi.org/10.3389/fimmu.2020.00730] [PMID: 32431699]

[76]
Dostert C, Grusdat M, Letellier E, Brenner D. The TNF family of ligands and receptors: communication modules in the immune system and beyond. Physiol Rev  2019; 99(1): 115-60.
 [http://dx.doi.org/10.1152/physrev.00045.2017] [PMID: 30354964]

[77]
McMillan D, Martinez-Fleites C, Porter J, et al. Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF. Nat Commun  2021; 12(1): 582.
 [http://dx.doi.org/10.1038/s41467-020-20828-3] [PMID: 33495441]

[78]
Park NR, Lim KE, Han MS, et al. Core binding factor β plays a critical role during chondrocyte differentiation. J Cell Physiol  2016; 231(1): 162-71.
 [http://dx.doi.org/10.1002/jcp.25068] [PMID: 26058470]

[79]
Rabie ABM, Tang GH, Hägg U. Cbfa1 couples chondrocytes maturation and endochondral ossification in rat mandibular condylar cartilage. Arch Oral Biol  2004; 49(2): 109-18.
 [http://dx.doi.org/10.1016/j.archoralbio.2003.09.006] [PMID: 14693204]

[80]
Hoemann CD, Tran-Khanh N, Chevrier A, et al. Chondroinduction is the main cartilage repair response to microfracture and microfracture with BST-CarGel: Results as shown by ICRS-II histological scoring and a novel zonal collagen type scoring method of human clinical biopsy specimens. Am J Sports Med  2015; 43(10): 2469-80.
 [http://dx.doi.org/10.1177/0363546515593943] [PMID: 26260465]

[81]
Zorzi A, Amstalden E, Plepis A, et al. Effect of human adipose tissue mesenchymal stem cells on the regeneration of ovine articular cartilage. Int J Mol Sci  2015; 16(11): 26813-31.
 [http://dx.doi.org/10.3390/ijms161125989] [PMID: 26569221]

[82]
Lee P, Tran K, Zhou G, et al. Guided differentiation of bone marrow stromal cells on co-cultured cartilage and bone scaffolds. Soft Matter  2015; 11(38): 7648-55.
 [http://dx.doi.org/10.1039/C5SM01909E] [PMID: 26292727]

[83]
Li S, Yang X, Tang S, Zhang X, Feng Z, Cui S. Repair of massively defected hemi-joints using demineralized osteoarticular allografts with protected cartilage. J Mater Sci Mater Med  2015; 26(8): 227.
 [http://dx.doi.org/10.1007/s10856-015-5557-5] [PMID: 26319778]

[84]
McMahon LA, O’Brien FJ, Prendergast PJ. Biomechanics and mechanobiology in osteochondral tissues. Regen Med  2008; 3(5): 743-59.
 [http://dx.doi.org/10.2217/17460751.3.5.743] [PMID: 18729798]

[85]
Yang X, Teguh D, Wu JP, et al. Protein kinase C delta null mice exhibit structural alterations in articular surface, intra-articular and subchondral compartments. Arthritis Res Ther  2015; 17(1): 210.
 [http://dx.doi.org/10.1186/s13075-015-0720-4] [PMID: 26279273]

[86]
Nomura M, Sakitani N, Iwasawa H, et al. Thinning of articular cartilage after joint unloading or immobilization. An experimental investigation of the pathogenesis in mice. Osteoarthr Cartil  2017; 25(5): 727-36.
 [http://dx.doi.org/10.1016/j.joca.2016.11.013] [PMID: 27916560]

[87]
Kaul G, Cucchiarini M, Remberger K, Kohn D, Madry H. Failed cartilage repair for early osteoarthritis defects: A biochemical, histological and immunohistochemical analysis of the repair tissue after treatment with marrow-stimulation techniques. Knee Surg Sports Traumatol Arthrosc  2012; 20(11): 2315-24.
 [http://dx.doi.org/10.1007/s00167-011-1853-x] [PMID: 22222614]

[88]
Hwang H, Kim H. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int J Mol Sci  2015; 16(11): 26035-54.
 [http://dx.doi.org/10.3390/ijms161125943] [PMID: 26528972]

[89]
Boscá L, Zeini M, Través P, Hortelano S. Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology  2005; 208(2): 249-58.
 [http://dx.doi.org/10.1016/j.tox.2004.11.035] [PMID: 15691589]

[90]
Singh P, Marcu KB, Goldring MB, Otero M. Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy. Ann N Y Acad Sci  2019; 1442(1): 17-34.
 [http://dx.doi.org/10.1111/nyas.13930] [PMID: 30008181]

[91]
Kim HA, Kim YH, Song YW. Facilitation of fas mediated apoptosis of human chondrocytes by the proteasome inhibitor and actinomycin D. J Rheumatol  2003; 30(3): 550-8.
 [PMID: 12610816]

[92]
Dideriksen K, Boesen AP, Reitelseder S, et al. Tendon collagen synthesis declines with immobilization in elderly humans: No effect of anti-inflammatory medication. J Appl Physiol  2017; 122(2): 273-82.
 [http://dx.doi.org/10.1152/japplphysiol.00809.2015] [PMID: 27932679]

[93]
Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of Apoptosis in disease. Aging (Albany NY)  2012; 4(5): 330-49.
 [http://dx.doi.org/10.18632/aging.100459] [PMID: 22683550]

[94]
Plotkin LI. Apoptotic osteocytes and the control of targeted bone resorption. Curr Osteoporos Rep  2014; 12(1): 121-6.
 [http://dx.doi.org/10.1007/s11914-014-0194-3] [PMID: 24470254]

[95]
Dinarello CA. Overview of the interleukin-1 family of ligands and receptors. Semin Immunol  2013; 25(6): 389-93.
 [http://dx.doi.org/10.1016/j.smim.2013.10.001] [PMID: 24275600]

[96]
Piccioli P, Rubartelli A. The secretion of IL-1β and options for release. Semin Immunol  2013; 25(6): 425-9.
 [http://dx.doi.org/10.1016/j.smim.2013.10.007] [PMID: 24201029]

[97]
Mei Y, Williams JS, Webb EK, Shea AK, MacDonald MJ, Al-Khazraji BK. Roles of hormone replacement therapy and menopause on osteoarthritis and cardiovascular disease outcomes: A narrative review. Front Rehabil Sci  2022; 3: 825147.
 [http://dx.doi.org/10.3389/fresc.2022.825147]

[98]
Physical activity pathway for patients with osteoarthritis in primary care (OA-PCP) (R33) (OA-PCP). Patent NCT04533711, 2022.

[99]
Study of Nonsteroidal Anti-inflammatory Drugs in People With Painful Knee Osteoarthritis. Patent NCT05430230, 2023.

[100]
PROs Following low-dose irradiation for osteoarthritis (PRO-LO). Patent NCT05705947, 2023.

[101]
pAF for the Treatment of Osteoarthritis. Patent NCT04886960, 2023.

[102]
Green P. Cannabinoid tablets for the treatment of pain from osteoarthritis of the knee. Patent NCT04992962, 2021.

[103]
Intraarticular Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis. Patent NCT05160532, 2023.

[104]
S-Asenosyl-L-Methionine vs Placebo for Osteoarthritis of the Hands (SAMe). Patent NCT05363020, 2023.

[105]
Cannabinoid interactions with central and peripheral pain mechanisms in osteoarthritis of the knee. Patent NCT04992624, 2023.

[106]
Safety & effectiveness of autologous regenerative cell therapy on pain & inflammation of osteoarthritis of the hip. Patent NCT02844764, 2021.

[107]
Maximizing analgesia to reduce pain in knee osteoarthritis. Patent NCT03098563, 2022.

[108]
Safety & effectiveness of autologous regenerative cell therapy on pain & inflammation of osteoarthritis of the shoulder. Patent NCT02844738, 2021.

[109]
Cannabidiol (CBD) in pain reduction for knee osteoarthritis. Patent NCT05020028, 2023.

[110]
Efficacy of PRGF Supplementation After TMJ Arthrocentesis in Patients With TMJ Osteoarthritis. Patent NCT04731233, 2023.

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DOI https://dx.doi.org/10.2174/1573397119666230904150741	Print ISSN 1573-3971
Publisher Name Bentham Science Publisher	Online ISSN 1875-6360

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