expression was significantly down-regulated in the synovial tissue of patients and in the ankle joints of CIA mice.
BMP9 treatment in CIA mice reduced joint inflammation, indicated by decreased limb swelling and lower arthritis index.
BMP9 significantly alleviated bone loss, as shown by increased bone mineral density and improved trabecular structure.
Treatment with BMP9 enhanced bone mineralization and formation, evidenced by increased mineral apposition rate and bone formation rate.
BMP9 promoted osteogenic differentiation of synovial cells, as indicated by enhanced alkaline phosphatase activity and mineral nodule formation.
BMP9 did not significantly influence osteoclast activity or bone resorption.
Simplified
OBJECTIVE: (RA) is a chronic inflammatory disorder that causes joint damage, including cartilage degradation and bone erosion. (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 METHODS: In 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.
RESULTS: In 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.
CONCLUSION: Our 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.
Key numbers
significantly lower
Decrease in Expression
expression in patients vs. OA patients
significantly lower
Lower Arthritis Index
Arthritis index in CIA mice treated with vs. untreated
significantly higher
Increase in Bone Formation Rate
Bone formation rate in -treated mice vs. CIA mice
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Declarations. Ethics approval and consent to participate: All participants in this study gave informed consent prior to their inclusion. The animal experiments were conducted in accordance with the National Research Council's Guide for the Care and Use of Laboratory Animals. The study protocols were approved by the Ethical Committee of the Affiliated Hospital of Qingdao University and the Animal Experimentation Ethics Committee of Qingdao University. Consent for publication: All authors gave their consent for publication and have no conflicts of interest. Competing interests: The authors declare that they have no competing interests.
