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Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematopoiesis through its receptor complex. In this review, we first describe the characteristics of OSM and its receptor, and the biological functions of OSM signaling. Subsequently, we discuss the possible roles of OSM in the development of RA from clinical and basic research perspectives. Finally, we summarize the progress of clinical studies targeting OSM for the treatment of RA. This review provides researchers with a systematic understanding of the role of OSM signaling in RA, which can guide the development of drugs targeting OSM for the treatment of RA.

SUBMITTER: Han L

PROVIDER: S-EPMC10654622 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis.

Han Liang L Yan Jiahui J Li Tingting T Lin Weiji W Huang Yao Y Shen Pan P Ba Xin X Huang Ying Y Qin Kai K Geng Yinhong Y Wang Huanhuan H Zheng Kaifeng K Liu Yafei Y Wang Yu Y Chen Zhe Z Tu Shenghao S

Frontiers in immunology 20231101

Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematop ...[more]

PMID: 38022540

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Project description:ObjectiveRheumatoid arthritis (RA) is a chronic inflammatory disorder that causes joint damage, including cartilage degradation and bone erosion. Bone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, plays a key role in osteogenesis and tissue repair. However, its role in bone erosion and inflammation in RA remains underexplored. This study aims to evaluate BMP9's therapeutic potential in RA, focusing on its effects on bone destruction, osteogenesis, and inflammation.Materials and methodsIn this study, BMP9 expression was analyzed in synovial tissues from RA and osteoarthritis patients and in the ankle joints of collagen-induced arthritis (CIA) mice using immunohistochemistry, qRT-PCR, and Western blotting. The therapeutic effect of BMP9 on bone destruction was evaluated in a CIA mouse model through micro-CT imaging, histological analysis, and clinical scoring. Osteogenic differentiation was assessed by alkaline phosphatase and Alizarin Red S staining, while osteoclast activity was examined through tartrate-resistant acid phosphatase staining. Fluorescence double-labeling was used to track new bone formation. Data were analyzed using (Statistical Package for the Social Sciences) SPSS, and appropriate statistical tests were performed to determine significance.ResultsIn this study, BMP9 expression was significantly down-regulated in the synovial tissue of RA patients and in the ankle joints of CIA mice. BMP9 treatment in CIA mice ameliorated joint inflammation, as shown by reduced limb swelling, lower arthritis index, and improved tissue morphology. Furthermore, BMP9 significantly alleviated bone loss, as evidenced by increased bone mineral density and trabecular structure. However, BMP9 treatment did not significantly impact osteoclastogenesis or bone resorption. BMP9 also enhanced bone mineralization and formation, as shown by increased mineral apposition rate and bone formation rate. Additionally, BMP9 promoted osteogenic differentiation of synovial cells, enhancing alkaline phosphatase activity and mineral nodule formation. These results suggest that BMP9 has a protective effect on joint inflammation and bone loss in RA, potentially through promoting bone formation without influencing osteoclast activity.ConclusionOur study concludes that targeting BMP9 alleviates inflammation and promotes osteogenic differentiation in RA, highlighting BMP9 as a promising therapeutic target for addressing bone destruction in RA.

Dataset Information

Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis.

Publications

Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis.

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