The potential roles of JAK/STAT signaling in the progression of osteoarthritis

Abstract

Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA is a complex process, and the risk factors are various, including aging, genetics, trauma and altered biomechanics. Inflammation and immunity play an important role in the pathogenesis of OA. JAK/STAT pathway is one of the most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, and apoptosis. Inflammatory factors can act as the initiators of JAK/STAT pathway, which is implicated in the pathophysiological activity of chondrocyte. In this article, we provide a review on the importance of JAK/STAT pathway in the pathological development of OA. Potentially, JAK/STAT pathway becomes a therapeutic target for managing OA.

Keywords: JAK/STAT pathway; SOCS; cartilage remodeling; inflammation; osteoarthritis.

Figure 1

JAK/STAT pathway can be stimulated by various cytokines. A lot of extracellular cytokines, such as IL-6, IL-4, and IL-10, can interact with the specific receptors, which phosphorylate JAKs and recruit STAT. Activated STAT forms dimer and enter the nucleus for mediating the transcriptional expression of target genes, such as inflammatory cytokines.

Figure 2

The implication of JAK/STAT pathway in the pathological development of OA. Active JAK/STAT pathway may induce the pathological development of OA by regulating inflammation, immune responses, mechanical loading, and apoptosis, leading to cartilage destruction, subchondral bone destruction, and synovial inflammation.

Figure 3

The potential mechanism of JAK/STAT pathway in OA development. Inflammation factors, such as IL-6, IL-4, and TNFα, in the OA cartilage can stimulate JAK/STAT pathway, which induces the destruction of OA cartilage, as shown by increased chondrocyte apoptosis and ECM degradation.