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Osteoarthritis year in review 2021: biology

  • Y. Jiang
    Correspondence
    Address correspondence and reprint requests to: Y. Jiang, Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Tel.: 852-39435153; fax: 852-26035123.
    Affiliations
    Institute for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

    School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

    Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
    Search for articles by this author
Published:November 18, 2021DOI:https://doi.org/10.1016/j.joca.2021.11.009

      Summary

      This year in review on osteoarthritis biology summarizes a series of research articles published between the 2020 and 2021 Osteoarthritis Research Society International (OARSI) World Congress. Research hightlights were selected and discussed based on the new discoveries of OA's cellular molecular mechanism, anatomical signatures, potential therapeutic targets, and regenerative therapy. The recently developed potential therapeutic targets are summarized, and the research focuses on TGFβ and WNT signaling in joint tissue homeostasis, joint aging and the dynamic of synolytics in OA joint, and the roles of TRP2, LDHA, OSCAR in cartilage homeostasis and OA joints are highlighted. Subsquencially, new anatomical structures and OA features are introduced, such as synovitis-induced venous portal circulation, horiozontal fissures between cartilage and subchondral bone, the cellular derivation of osteophytes formation, OA subtypes, and subchondral remodeling and pain biology. Then, research on the possibility of tissue regeneration in OA joints are discussed; skeletal stem cells in OA cartilage regeneration, and preclinical results of regenerative therapy for meniscus tear and osteochondral tissue morphoghesis are included. At last, the clinical evidence of the importance of delivery site of bone marrow stem cells for OA treatment is discussed. These findings represent advances in our understanding of OA pathophysiology.

      Keywords

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      References
      Research articles published between April 2020–April 2021.

        • Wang C.
        • Shen J.
        • Ying J.
        • Xiao D.
        • O'Keefe R.J.
        FoxO 1 is a crucial mediator of TGF-beta/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis.
        Proc Natl Acad Sci U S A. 2020; 117 (Epub 2020/11/18. PubMed PMID: 33199631; PubMed Central PMCID: PMCPMC7720227): 30488-30497https://doi.org/10.1073/pnas.2017056117
        • Wang G.
        • Chen S.
        • Xie Z.
        • Shen S.
        • Xu W.
        • Chen W.
        • et al.
        TGFβ attenuates cartilage extracellular matrix degradation via enhancing FBXO6-mediated MMP14 ubiquitination.
        Ann Rheum Dis. 2020; 79: 1111-1120https://doi.org/10.1136/annrheumdis-2019-216911
        • Zhen G.
        • Guo Q.
        • Li Y.
        • Wu C.
        • Zhu S.
        • Wang R.
        • et al.
        Mechanical stress determines the configuration of TGFbeta activation in articular cartilage.
        Nat Commun. 2021; 12 (Epub 2021/03/19. PubMed PMID: 33731712; PubMed Central PMCID: PMCPMC7969741): 1706https://doi.org/10.1038/s41467-021-21948-0
        • Bailey K.N.
        • Nguyen J.
        • Yee C.S.
        • Dole N.S.
        • Dang A.
        • Alliston T.
        Mechanosensitive control of articular cartilage and subchondral bone homeostasis in mice requires osteocytic transforming growth factor beta signaling.
        Arthritis Rheum. 2021; 73 (Epub 2020/10/07. PubMed PMID: 33022131): 414-425https://doi.org/10.1002/art.41548
        • Bertrand J.
        • Kraft T.
        • Gronau T.
        • Sherwood J.
        • Rutsch F.
        • Liote F.
        • et al.
        BCP crystals promote chondrocyte hypertrophic differentiation in OA cartilage by sequestering Wnt3a.
        Ann Rheum Dis. 2020; 79 (Epub 2020/05/07. PubMed PMID: 32371389): 975-984https://doi.org/10.1136/annrheumdis-2019-216648
        • Thorup A.S.
        • Strachan D.
        • Caxaria S.
        • Poulet B.
        • Thomas B.L.
        • Eldridge S.E.
        • et al.
        ROR2 blockade as a therapy for osteoarthritis.
        Sci Transl Med. 2020; 12 (Epub 2020/09/18. PubMed PMID: 32938794)https://doi.org/10.1126/scitranslmed.aax3063
        • Conaghan P.G.
        • Hunter D.J.
        • Cohen S.B.
        • Kraus V.B.
        • Berenbaum F.
        • Lieberman J.R.
        • et al.
        Effects of a single intra-articular injection of a microsphere formulation of triamcinolone acetonide on knee osteoarthritis pain: a double-blinded, randomized, placebo-controlled, multinational study.
        J Bone Joint Surg Am. 2018; 100 (Epub 2018/04/18. PubMed PMID: 29664853; PubMed Central PMCID: PMCPMC5916484): 666-677https://doi.org/10.2106/JBJS.17.00154
        • Pelletier J.P.
        • Yaron M.
        • Haraoui B.
        • Cohen P.
        • Nahir M.A.
        • Choquette D.
        • et al.
        Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group.
        Arthritis Rheum. 2000; 43 (Epub 2000/10/19. PubMed PMID: 11037895): 2339-2348https://doi.org/10.1002/1529-0131(200010)43:10<2339::AID-ANR23>3.0.CO;2-P
        • Dougados M.
        • Nguyen M.
        • Berdah L.
        • Mazieres B.
        • Vignon E.
        • Lequesne M.
        • et al.
        Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip.
        Arthritis Rheum. 2001; 44 (Epub 2001/11/17. PubMed PMID: 11710710): 2539-2547https://doi.org/10.1002/1529-0131(200111)44:11<2539::aid-art434>3.0.co;2-t
        • Cardiel M.H.
        • Tak P.P.
        • Bensen W.
        • Burch F.X.
        • Forejtova S.
        • Badurski J.E.
        • et al.
        A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis.
        Arthritis Res Ther. 2010; 12 (Epub 2010/10/19. PubMed PMID: 20950476; PubMed Central PMCID: PMCPMC2991028): R192https://doi.org/10.1186/ar3163
        • Cohen S.B.
        • Proudman S.
        • Kivitz A.J.
        • Burch F.X.
        • Donohue J.P.
        • 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 (Epub 2011/08/02. PubMed PMID: 21801403; PubMed Central PMCID: PMCPMC3239365): R125https://doi.org/10.1186/ar3430
        • Kamiya N.
        • Kuroyanagi G.
        • Aruwajoye O.
        • Kim H.K.W.
        IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice.
        Osteoarthritis Cartilage. 2019; 27 (Epub 2018/11/08. PubMed PMID: 30404032): 326-335https://doi.org/10.1016/j.joca.2018.10.010
        • Lee K.M.
        • Prasad V.
        • Achuthan A.
        • Fleetwood A.J.
        • Hamilton J.A.
        • Cook A.D.
        Targeting GM-CSF for collagenase-induced osteoarthritis pain and disease in mice.
        Osteoarthritis Cartilage. 2020; 28 (Epub 2020/02/07. PubMed PMID: 32028021): 486-491https://doi.org/10.1016/j.joca.2020.01.012
        • Conaghan P.G.
        • Cook A.D.
        • Hamilton J.A.
        • Tak P.P.
        Therapeutic options for targeting inflammatory osteoarthritis pain.
        Nat Rev Rheumatol. 2019; 15 (Epub 2019/05/10. PubMed PMID: 31068673): 355-363https://doi.org/10.1038/s41584-019-0221-y
        • Hochberg M.C.
        • Guermazi A.
        • Guehring H.
        • Aydemir A.
        • Wax S.
        • Fleuranceau-Morel P.
        • et al.
        Effect of intra-articular sprifermin vs placebo on femorotibial joint cartilage thickness in patients with osteoarthritis: the FORWARD randomized clinical trial.
        JAMA. 2019; 322 (Epub 2019/10/09. PubMed PMID: 31593273; PubMed Central PMCID: PMCPMC6784851): 1360-1370https://doi.org/10.1001/jama.2019.14735
        • Kim M.K.
        • Ha C.W.
        • In Y.
        • Cho S.D.
        • Choi E.S.
        • Ha J.K.
        • et al.
        A multicenter, double-blind, phase III clinical trial to evaluate the efficacy and safety of a cell and gene therapy in knee osteoarthritis patients.
        Hum Gene Ther Clin Dev. 2018; 29 (Epub 2018/04/12. PubMed PMID: 29641281): 48-59https://doi.org/10.1089/humc.2017.249
        • Faust H.J.
        • Zhang H.
        • Han J.
        • Wolf M.T.
        • Jeon O.H.
        • Sadtler K.
        • et al.
        IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis.
        J Clin Invest. 2020; 130 (Epub 2020/09/22. PubMed PMID: 32955487; PubMed Central PMCID: PMCPMC7524483): 5493-5507https://doi.org/10.1172/JCI134091
        • Jiang Y.
        • Tuan R.S.
        Origin and function of cartilage stem/progenitor cells in osteoarthritis.
        Nat Rev Rheumatol. 2015; 11 (Epub 2014/12/24. PubMed PMID: 25536487; PubMed Central PMCID: PMCPMC5413931): 206-212https://doi.org/10.1038/nrrheum.2014.200
        • Jiang Y.
        • Cai Y.
        • Zhang W.
        • Yin Z.
        • Hu C.
        • Tong T.
        • et al.
        Human cartilage-derived progenitor cells from committed chondrocytes for efficient cartilage repair and regeneration.
        Stem Cells Transl Med. 2016; 5 (Epub 2016/05/01. PubMed PMID: 27130221; PubMed Central PMCID: PMCPMC4878331): 733-744https://doi.org/10.5966/sctm.2015-0192
        • Gupta P.K.
        • Chullikana A.
        • Rengasamy M.
        • Shetty N.
        • Pandey V.
        • Agarwal V.
        • et al.
        Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel(R)): preclinical and clinical trial in osteoarthritis of the knee joint.
        Arthritis Res Ther. 2016; 18 (Epub 2016/12/21. PubMed PMID: 27993154; PubMed Central PMCID: PMCPMC5168586): 301https://doi.org/10.1186/s13075-016-1195-7
        • Lu L.
        • Dai C.
        • Zhang Z.
        • Du H.
        • Li S.
        • Ye P.
        • et al.
        Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial.
        Stem Cell Res Ther. 2019; 10 (Epub 2019/05/23. PubMed PMID: 31113476; PubMed Central PMCID: PMCPMC6528322): 143https://doi.org/10.1186/s13287-019-1248-3
        • Murphy M.P.
        • Koepke L.S.
        • Lopez M.T.
        • Tong X.
        • Ambrosi T.H.
        • Gulati G.S.
        • et al.
        Articular cartilage regeneration by activated skeletal stem cells.
        Nat Med. 2020; 26 (Epub 2020/08/19. PubMed PMID: 32807933; PubMed Central PMCID: PMCPMC7704061.): 1583-1592https://doi.org/10.1038/s41591-020-1013-2
        • Lee K.I.
        • Gamini R.
        • Olmer M.
        • Ikuta Y.
        • Hasei J.
        • Baek J.
        • et al.
        Mohawk is a transcription factor that promotes meniscus cell phenotype and tissue repair and reduces osteoarthritis severity.
        Sci Transl Med. 2020; 12 (Epub 2020/10/30. PubMed PMID: 33115953; PubMed Central PMCID: PMCPMC7955769)https://doi.org/10.1126/scitranslmed.aan7967
        • Eldridge S.E.
        • Barawi A.
        • Wang H.
        • Roelofs A.J.
        • Kaneva M.
        • Guan Z.
        • et al.
        Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis.
        Sci Transl Med. 2020; 12 (Epub 2020/09/04. PubMed PMID: 32878982)https://doi.org/10.1126/scitranslmed.aax9086
        • Roelofs A.J.
        • Kania K.
        • Rafipay A.J.
        • Sambale M.
        • Kuwahara S.T.
        • Collins F.L.
        • et al.
        Identification of the skeletal progenitor cells forming osteophytes in osteoarthritis.
        Ann Rheum Dis. 2020; 79 (Epub 2020/09/24. PubMed PMID: 32963046; PubMed Central PMCID: PMCPMC8136618): 1625-1634https://doi.org/10.1136/annrheumdis-2020-218350
        • Reginster J.Y.
        • Badurski J.
        • Bellamy N.
        • Bensen W.
        • Chapurlat R.
        • Chevalier X.
        • et al.
        Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial.
        Ann Rheum Dis. 2013; 72 (Epub 2012/11/03. PubMed PMID: 23117245; PubMed Central PMCID: PMCPMC3599139): 179-186https://doi.org/10.1136/annrheumdis-2012-202231
        • Bruyere O.
        • Reginster J.Y.
        • Bellamy N.
        • Chapurlat R.
        • Richette P.
        • Cooper C.
        • et al.
        Clinically meaningful effect of strontium ranelate on symptoms in knee osteoarthritis: a responder analysis.
        Rheumatology (Oxford). 2014; 53 (Epub 2014/03/29. PubMed PMID: 24667161): 1457-1464https://doi.org/10.1093/rheumatology/keu018
        • Sun Q.
        • Zhen G.
        • Li T.P.
        • Guo Q.
        • Li Y.
        • Su W.
        • et al.
        Parathyroid hormone attenuates osteoarthritis pain by remodeling subchondral bone in mice.
        Elife. 2021; 10 (Epub 2021/03/02. PubMed PMID: 33646122; PubMed Central PMCID: PMCPMC8012060)https://doi.org/10.7554/eLife.66532
        • Hayes K.N.
        • Giannakeas V.
        • Wong A.K.O.
        Bisphosphonate use is protective of radiographic knee osteoarthritis progression among those with low disease severity and being non-overweight: data from the osteoarthritis initiative.
        J Bone Miner Res. 2020; 35 (Epub 2020/07/15. PubMed PMID: 32662919): 2318-2326https://doi.org/10.1002/jbmr.4133
        • Conaghan P.G.
        • Bowes M.A.
        • Kingsbury S.R.
        • Brett A.
        • Guillard G.
        • Rizoska B.
        • et al.
        Disease-modifying effects of a novel cathepsin K inhibitor in osteoarthritis: a randomized controlled trial.
        Ann Intern Med. 2020; 172 (Epub 2019/12/31. PubMed PMID: 31887743): 86-95https://doi.org/10.7326/M19-0675
        • Walsh D.A.
        • Neogi T.
        A tale of two TrkA inhibitor trials: same target, divergent results.
        Osteoarthritis Cartilage. 2019; 27 (Epub 2019/07/30. PubMed PMID: 31356877; PubMed Central PMCID: PMCPMC6941477): 1575-1577https://doi.org/10.1016/j.joca.2019.07.013
        • Stevens R.M.
        • Ervin J.
        • Nezzer J.
        • Nieves Y.
        • Guedes K.
        • Burges R.
        • et al.
        Randomized, double-blind, placebo-controlled trial of intraarticular trans-capsaicin for pain associated with osteoarthritis of the knee.
        Arthritis Rheum. 2019; 71 (Epub 2019/03/20. PubMed PMID: 30888737; PubMed Central PMCID: PMCPMC6772016): 1524-1533https://doi.org/10.1002/art.40894
        • Afzal A.R.
        • Jeffery S.
        One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B.
        Hum Mutat. 2003; 22 (Epub 2003/06/20. PubMed PMID: 12815588): 1-11https://doi.org/10.1002/humu.10233
        • Nakamoto H.
        • Katanosaka Y.
        • Chijimatsu R.
        • Mori D.
        • Xuan F.
        • Yano F.
        • et al.
        TRPV2 is involved in induction of lubricin and suppression of ectopic endochondral ossification in articular joints.
        Arthritis Rheum. 2021; (Epub 2021/02/16. PubMed PMID: 33586252)https://doi.org/10.1002/art.41684
        • Arra M.
        • Swarnkar G.
        • Ke K.
        • Otero J.E.
        • Ying J.
        • Duan X.
        • et al.
        LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis.
        Nat Commun. 2020; 11 (Epub 2020/07/11. PubMed PMID: 32647171; PubMed Central PMCID: PMCPMC7347613): 3427https://doi.org/10.1038/s41467-020-17242-0
        • Park D.R.
        • Kim J.
        • Kim G.M.
        • Lee H.
        • Kim M.
        • Hwang D.
        • et al.
        Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation.
        Nat Commun. 2020; 11 (Epub 2020/08/30. PubMed PMID: 32859940; PubMed Central PMCID: PMCPMC7455568): 4343https://doi.org/10.1038/s41467-020-18208-y
        • Sayed N.
        • Huang Y.
        • Nguyen K.
        • Krejciova-Rajaniemi Z.
        • Grawe A.P.
        • Gao T.
        • et al.
        An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging.
        Nature Aging. 2021; 1: 598-615https://doi.org/10.1038/s43587-021-00082-y
        • Seeherman H.J.
        • Li X.J.
        • Wozney J.M.
        Activation of bone remodeling compartments in BMP-2-injected knees supports a local vascular mechanism for arthritis-related bone changes.
        J Bone Joint Surg Am. 2021; 103 (Epub 2020/12/15. PubMed PMID: 33315697): e8https://doi.org/10.2106/JBJS.20.00883
        • Chen L.
        • Yao F.
        • Wang T.
        • Li G.
        • Chen P.
        • Bulsara M.
        • et al.
        Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis.
        Ann Rheum Dis. 2020; 79 (Epub 2020/04/10. PubMed PMID: 32269059; PubMed Central PMCID: PMCPMC7286031): 811-818https://doi.org/10.1136/annrheumdis-2020-216942
        • Karsdal M.A.
        • Christiansen C.
        • Ladel C.
        • Henriksen K.
        • Kraus V.B.
        Bay-Jensen AC. Osteoarthritis--a case for personalized health care?.
        Osteoarthritis Cartilage. 2014; 22 (Epub 2013/11/13. PubMed PMID: 24216058): 7-16https://doi.org/10.1016/j.joca.2013.10.018
        • Herrero-Beaumont G.
        • Roman-Blas J.A.
        • Bruyere O.
        • Cooper C.
        • Kanis J.
        • Maggi S.
        • et al.
        Clinical settings in knee osteoarthritis: pathophysiology guides treatment.
        Maturitas. 2017; 96 (Epub 2017/01/04. PubMed PMID: 28041596): 54-57https://doi.org/10.1016/j.maturitas.2016.11.013
        • Yuan C.
        • Pan Z.
        • Zhao K.
        • Li J.
        • Sheng Z.
        • Yao X.
        • et al.
        Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas.
        Bone Res. 2020; 8 (Epub 2020/12/11. PubMed PMID: 33298863; PubMed Central PMCID: PMCPMC7658991): 38https://doi.org/10.1038/s41413-020-00109-x
        • Zhu X.
        • Chan Y.T.
        • Yung P.S.H.
        • Tuan R.S.
        • Jiang Y.
        Subchondral bone remodeling: a therapeutic target for osteoarthritis.
        Front Cell Dev Biol. 2020; 8 (Epub 2021/02/09. PubMed PMID: 33553146; PubMed Central PMCID: PMCPMC7859330): 607764https://doi.org/10.3389/fcell.2020.607764
        • Aso K.
        • Shahtaheri S.M.
        • Hill R.
        • Wilson D.
        • McWilliams D.F.
        • Nwosu L.N.
        • et al.
        Contribution of nerves within osteochondral channels to osteoarthritis knee pain in humans and rats.
        Osteoarthritis Cartilage. 2020; 28 (Epub 2020/05/30. PubMed PMID: 32470596): 1245-1254https://doi.org/10.1016/j.joca.2020.05.010
        • Zhu J.
        • Zhen G.
        • An S.
        • Wang X.
        • Wan M.
        • Li Y.
        • et al.
        Aberrant subchondral osteoblastic metabolism modifies NaV1.8 for osteoarthritis.
        Elife. 2020; 9 (Epub 2020/05/23. PubMed PMID: 32441256; PubMed Central PMCID: PMC7308086)https://doi.org/10.7554/eLife.57656
        • Hernigou P.
        • Bouthors C.
        • Bastard C.
        • Flouzat Lachaniette C.H.
        • Rouard H.
        • Dubory A.
        Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study.
        Int Orthop. 2021; 45 (Epub 2020/07/04. PubMed PMID: 32617651): 391-399https://doi.org/10.1007/s00264-020-04687-7
        • Hernigou P.
        • Delambre J.
        • Quiennec S.
        • Poignard A.
        Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteen year follow-up.
        Int Orthop. 2021; 45 (Epub 2020/04/24. PubMed PMID: 32322943): 365-373https://doi.org/10.1007/s00264-020-04571-4