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  • Title: The naturally derived small compound Osthole inhibits osteoclastogenesis to prevent ovariectomy-induced bone loss in mice.
    Author: Zhao D, Wang Q, Zhao Y, Zhang H, Sha N, Tang D, Liu S, Lu S, Shi Q, Zhang Y, Dong Y, Wang Y, Shu B.
    Journal: Menopause; 2018 Dec; 25(12):1459-1469. PubMed ID: 29944638.
    Abstract:
    OBJECTIVE: This study was to determine the bone protective effects and underlying mechanisms of Osthole (OT) in ovariectomized (OVX) mice. We found that the inhibitory effects of OT on receptor activator of nuclear factor kappa-B ligand (RANKL)-activated osteoclastogenesis are responsible for its bone protective effects in OVX mice. METHODS: Eight-week-old mice were ovariectomized and OT (10 mg/kg/d) was intraperitoneally administrated to OVX mice 7 days after the surgery and were sacrificed at the end of the 3 months. Osteoclasts were generated from primary bone marrow macrophages (BMMs) to investigate the inhibitory effects of OT. The activity of RANKL-activated signaling was simultaneously analyzed in vitro and in vivo using immunohistochemistry, Western blot, and PCR assays. RESULTS: OT dose dependently inhibited RANKL-mediated osteoclastogenesis in BMM cultures. OT administration attenuated bone loss (mg Ha/cm: 894.68 ± 33.56 vs 748.08 ± 19.51, P < 0.05) in OVX mice. OT inhibits osteoclastogenesis (Oc.N/per view area: 72 ± 4.3 vs 0.8 ± 0.4, P < 0.05) and bone resorption activity (bone resorbed percentages %, 48.56 ± 7.25 vs 3.25 ± 1.37, P < 0.05) from BMMs. Mechanistically, OT inhibited the expressions of nuclear factor of activated T-cells c1 (NFATc1) and c-Fos. Moreover, OT suppressed the expression of RANKL-induced osteoclast marker genes, including matrix metalloproteinase 9 (MMP9), Cathepsin K (Ctsk), tartrate-resistant acid phosphatase (TRAP), and carbonic anhydrase II (Car2). CONCLUSIONS: OT inhibits RANKL-mediated osteoclastogenesis and prevents bone loss in OVX mice. Our findings revealed that OT is a potential new drug for treating postmenopausal osteoporosis.
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