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

Abstract

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.

Fig. 1. Pharmacological management of OA by blocking pro-inflammatory cytokines and matrix-degrading enzymes.

IL-1 and TNF are the major pro-inflammatory cytokines that stimulate the production of matrix-degrading enzymes and inflammatory mediators in joint tissues. MMP and ADAMTS family members degrade the extracellular matrix components of cartilage, promoting osteoarthritic cartilage destruction.