Abstract
AbstractOsteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and constitutes a considerable socioeconomic burden. Currently, pharmacological treatments mostly aim to relieve the OA symptoms associated with inflammation and pain. However, with increasing understanding of OA pathology, several potential therapeutic targets have been identified, enabling the development of disease-modifying OA drugs (DMOADs). By targeting inflammatory cytokines, matrix-degrading enzymes, the Wnt pathway, and OA-associated pain, DMOADs successfully modulate the degenerative changes in osteoarthritic cartilage. Moreover, regenerative approaches aim to counterbalance the loss of cartilage matrix by stimulating chondrogenesis in endogenous stem cells and matrix anabolism in chondrocytes. Emerging strategies include the development of senolytic drugs or RNA therapeutics to eliminate the cellular or molecular sources of factors driving OA. This review describes the current developmental status of DMOADs and the corresponding results from preclinical and clinical trials and discusses the potential of emerging therapeutic approaches to treat OA.
Funder
National Research Foundation of Korea
Ministry of Science, ICT and Future Planning
Suh Kyungbae foundation
Publisher
Springer Science and Business Media LLC
Subject
Clinical Biochemistry,Molecular Biology,Molecular Medicine,Biochemistry
Reference147 articles.
1. Kim, J. H. et al. Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis. Cell 156, 730–743 (2014).
2. Kang, D. et al. Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development. Sci. Transl. Med. 11, eaar6659 (2019).
3. Kim, S. et al. Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation. Nat. Commun. 10, 4898 (2019).
4. Mobasheri, A. et al. The role of metabolism in the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 13, 302–311 (2017).
5. Goldring, S. R. & Goldring, M. B. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk. Nat. Rev. Rheumatol. 12, 632–644 (2016).
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