Adipokines: New Therapeutic Target for Osteoarthritis?

Abstract

Purpose of the Review-Osteoarthritis (OA) is an aging-associated and injury-induced joint disease characterized by cartilage degradation, bone sclerosis, and persistent low-grade inflammation in the joint. Aging and injury are triggers of joint pathological changes mediated by pro-inflammatory factors, some of which are secreted by white adipose tissue. Adipokines including adiponectin, leptin, resistin, chemerin, IL-6, and TNF-α are major players not only during inflammation but also in metabolic regulation of joint cells including chondrocytes, osteoblasts, osteoclasts as well as mesenchymal stem cells. The purpose of this review is to summarize the signal transduction pathways of adipokines in the articular joint to provide new information on potential targets for intervention of OA. Recent Findings-The risk of knee osteoarthritis is associated with adipokine gene polymorphism. While the infrapatellar fat pad is a major source of adipokines in knee synovial fluid, adipocytes also accumulate in the bone marrow during aging and obesity. Adipokines can act as SASPs (senescence associated secretory phenotype factors) that participate in cellular senescence of chondrocytes, but they also regulate energy metabolism impacting bone remodeling. Thus, adipokines are closely related to the metabolic syndrome and degenerative pathological changes in cartilage and bone during OA. Summary-Modulating the effects of adipokines on different cell types in the intra-articular joint will be a promising new option for OA intervention.

GRB10 and E2F3 as Diagnostic Markers of Osteoarthritis and Their Correlation with Immune Infiltration

“…OA is a chronic joint disease that causes cartilage degradation, synovial inflammation, subchondral bone remodeling, and osteophyte formation [25]. Due to the lack of early diagnostic indicators, patients with OA often lose the best opportunity for treatment, resulting in a poor prognosis.…”

Resistin enhances IL‐1β and TNF‐α expression in human osteoarthritis synovial fibroblasts by inhibiting miR‐149 expression via the MEK and ERK pathways

“…Of the wide variety of animal models of that are available for studying the pathogenesis of OA, none can be fully extrapolated to the human condition of OA; the data suggest that different models relate to particular subtypes of OA, with distinct molecular mechanisms in joint structural damage and pain that depend on how OA is induced 37 . Adipokines, including resistin, have recently been acknowledged as being major players in OA‐induced degenerative changes in cartilage and bone 38 . Elevated local and systemic resistin levels in the early stages of trauma‐induced OA are likely due to increased expression of resistin by resident macrophage cells in the synovium, which directly affects cartilage matrix turnover and cytokine production 38 .…”

“…Adipokines, including resistin, have recently been acknowledged as being major players in OA‐induced degenerative changes in cartilage and bone 38 . Elevated local and systemic resistin levels in the early stages of trauma‐induced OA are likely due to increased expression of resistin by resident macrophage cells in the synovium, which directly affects cartilage matrix turnover and cytokine production 38 . Thus, resistin is thought to be important in the OA disease process that manifests in the first several weeks following joint injury 39 …”

Epidemiological study on the relationship among menopausal condition, bone fragility, and knee osteoarthritis

“…In ammation is generally induced by microfragments of cartilages or danger-associated molecular pattern (DAMPS) in synovial uids and releases several proteases and cytokines, which accelerate the degeneration of articular tissues [38][39][40] . The infrapatellar fat pad is a major source of adiponectin in synovial uid; adiponectins are closely related to the metabolic syndrome and degenerative pathological changes in the cartilage and bone during OA 41 . In this study, the presence of EKOA and DKOA correlated with an increasing serum hyaluronan concentration, which indicated synovitis, severity of knee OA, and degree of pain 23,42 ; this predicts future joint space narrowing over 5 years 43 .…”