Unlocking Bone Health: How Syringin Inhibits Osteoclasts via PTGS1 in Postmenopausal Osteoporosis

Background: Postmenopausal osteoporosis (PMOP) is a common metabolic bone disease resulting from excessive osteoclast activity, characterized by reduced bone mineral density and increased fracture risk. Syringin (SRG), a natural phenylpropanoid glycoside, has shown potential anti-osteoporotic effects; however, its molecular mechanism remains unclear. This study investigated whether SRG inhibits osteoclast differentiation through regulating prostaglandin-endoperoxide synthase 1 (PTGS1).Methods: RAW 264.7 cells were induced with receptor activator of nuclear factor-κB ligand (RANKL) and treated with SRG at 0, 2.5, 5, and 10 μM. Osteoclast differentiation was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and F-actin ring staining. The mRNA levels of cathepsin K (CTSK), matrix metalloproteinase-9 (Mmp9), and nuclear factor of activated T cells 1 (NFATc1) were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and PTGS1 (also known as COX1) protein expression was detected by Western Blot (WB). PTGS1 expression was regulated to assess its role in SRG-mediated effects. In vivo, an ovariectomized (OVX) rat model was established, and SRG was administered orally at 25 and 50 mg/kg for 8 weeks. Bone mineral density, serum biomarkers (TRAP, alkaline phosphatase ALP, alanine aminotransferase ALT, aspartate aminotransferase AST), and femoral histopathology were analyzed.Results: SRG significantly inhibited RANKL-induced osteoclast differentiation, accompanied by reduced expression of PTGS1, CTSK, Mmp9 and NFATc1 (p < 0.01). PTGS1 overexpression partially reversed these inhibitory effects of SRG (p < 0.05), supporting the involvement of PTGS1 in SRG-mediated regulation of osteoclast differentiation. In the OVX-induced PMOP rat model, SRG treatment increased femoral density (p < 0.01), reduced serum levels of TRAP, ALP and AST (p < 0.05), and improved bone tissue structure.Conclusion: SRG effectively inhibits osteoclast differentiation and mitigates OVX-induced osteoporosis via PTGS1, positioning it as a potential candidate compound for PMOP.