Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions

• Published in: Experimental & molecular medicine 2021, 53(0), , pp.1-8
• Main Authors: Cho, Yongsik, Jeong, Sumin, Kim, Hyeonkyeong, Kang, Donghyun, Lee, Jeeyeon, Kang, Seung-Baik, Kim, Jin-Hong
• Format: Article
• Language: English
• Subjects: 64/60; 692/308/575; 692/699/1670/407; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Arthritis; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cartilage; Cartilage (articular); Cartilage diseases; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Chondrocytes; Chondrogenesis; Chronic pain; Clinical trials; Combined Modality Therapy - methods; Cytokines; Cytokines - metabolism; Disease control; Disease Management; Disease Susceptibility; Drug delivery; Drug Development; Drug therapy; Humans; Inflammation; Medical Biochemistry; Molecular Medicine; Molecular Targeted Therapy; Osteoarthritis; Osteoarthritis - diagnosis; Osteoarthritis - etiology; Osteoarthritis - metabolism; Osteoarthritis - therapy; Pain; Review; Review Article; Signal Transduction - drug effects; Stem Cells; Therapeutic targets; Wnt protein; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-021-00710-y

Osteoarthritis (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. Osteoarthritis: moving from symptom relief towards disease control Researchers are exploring several promising avenues to develop treatments for osteoarthritis that control or reverse its progress, rather than simply relieving the symptoms of inflammation and pain. These new opportunities are emerging from increased understanding of the molec_reular mechanisms underlying the onset and progression of osteoarthritis. Seung-Baik Kang, Jin-Hong Kim and colleagues at Seoul National University, South Korea, review the current status and future directions of disease-modifying strategies that are already showing promise in clinical trials. They discuss approaches aimed at restricting the damage to joint cartilage by controlling the inflammatory signaling molecules, enzyme actions and molecular pathways that cause cartilage to degenerate. They also consider treatments that could stimulate the active regeneration of damaged cartilage. They conclude that some approaches will soon be ready to move into general clinical use.