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Review
. 2022 Nov 24:13:1069057.
doi: 10.3389/fendo.2022.1069057. eCollection 2022.

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

Qingluo Zhou  1 , Qun Ren  2 , Linhui Jiao  2 , Jishang Huang  1 , Jun Yi  1 , Jincai Chen  1 , Jinliang Lai  1 , Guanglin Ji  1 , Tiansheng Zheng  1
Affiliations
Review

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

Qingluo Zhou et al. Front Endocrinol (Lausanne). .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
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
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
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.
See this image and copyright information in PMC

References

    1. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol (2011) 7(1):33–42. doi: 10.1038/nrrheum.2010.196 - DOI - PubMed
    1. Mastbergen SC, Lafeber FP. Changes in subchondral bone early in the development of osteoarthritis. Arthritis Rheum (2011) 63(9):2561–3. doi: 10.1002/art.30306 - DOI - PubMed
    1. Moon PM, Beier F. Novel insights into osteoarthritis joint pathology from studies in mice. Curr Rheumatol Rep (2015) 17(8):50. doi: 10.1007/s11926-015-0524-1 - DOI - PubMed
    1. Singh P, Marcu KB, Goldring MB, Otero M. Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy. Ann N Y Acad Sci (2019) 1442(1):17–34. doi: 10.1111/nyas.13930 - DOI - PubMed
    1. Almonte-Becerril M, Navarro-Garcia F, Gonzalez-Robles A, Vega-Lopez MA, Lavalle C, Kouri JB. Cell death of chondrocytes is a combination between apoptosis and autophagy during the pathogenesis of osteoarthritis within an experimental model. Apoptosis (2010) 15(5):631–8. doi: 10.1007/s10495-010-0458-z - DOI - PubMed

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