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.

As an essential nutrient and trace element, selenium is required for living organisms and its beneficial roles in human health have been well recognized. The role of selenium is mainly played through selenoproteins synthesized by the selenium metabolic system. Selenoproteins have a wide range of cellular functions including regulation of selenium transport, thyroid hormones, immunity, and redox homeostasis. Selenium deficiency contributes to various diseases, such as cardiovascular disease, cancer, liver disease, and arthropathy—Kashin–Beck disease (KBD) and osteoarthritis (OA). A skeletal developmental disorder, KBD has been reported in low-selenium areas of China, North Korea, and the Siberian region of Russia, and can be alleviated by selenium supplementation. OA, the most common form of arthritis, is a degenerative disease caused by an imbalance in matrix metabolism and is characterized by cartilage destruction. Oxidative stress serves as a major cause of the initiation of OA pathogenesis. Selenium deficiency and dysregulation of selenoproteins are associated with impairments to redox homeostasis in cartilage. We review the recently explored roles of selenium metabolism and selenoproteins in cartilage with an emphasis on two arthropathies, KBD and OA. Moreover, we discuss the potential of therapeutic strategies targeting the biological functions of selenium and selenoproteins for OA treatment.

Senescence-induced miR-204 alters the proteoglycan biosynthesis pathway and disrupts matrix homeostasis in osteoarthritic cartilage.

Significance: Osteoarthritic cartilage destruction is caused primarily by an imbalance between chondrocyte catabolism and anabolism. Various proinflammatory cytokines that disrupt this metabolic balance during osteoarthritis (OA) pathogenesis have been identified. Here, in addition to these biochemical pathways, we demonstrate that changes in the biophysical properties of the chondrocyte microenvironment triggered by cartilage matrix cross-linking play a causal role in OA pathogenesis. Two major OA risk factors, aging and mechanical stress, cause matrix stiffening via nonenzymatic and enzymatic collagen cross-linking through the accumulation of advanced glycation end-products and the upregulation of lysyl oxidase, respectively. Data from the current study illustrate the dynamic nature of physical remodeling of cartilage ECM and elucidate the key mechanotransduction pathway regulating chondrocyte metabolism and osteoarthritic cartilage destruction.