Tags

Type your tag names separated by a space and hit enter

The naturally derived small compound Osthole inhibits osteoclastogenesis to prevent ovariectomy-induced bone loss in mice.
Menopause. 2018 12; 25(12):1459-1469.M

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.

Authors+Show Affiliations

Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.Department of Orthopaedic Surgery, Louisiana State University Health Sciences Center, Shreveport, LA.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China. School of Rehabilitation Science, Shanghai University of TCM, Shanghai, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine (TCM), Shanghai, China. Spine Research Institute, Shanghai University of TCM, Shanghai, China. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of TCM), Shanghai, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29944638

Citation

Zhao, Dongfeng, et al. "The Naturally Derived Small Compound Osthole Inhibits Osteoclastogenesis to Prevent Ovariectomy-induced Bone Loss in Mice." Menopause (New York, N.Y.), vol. 25, no. 12, 2018, pp. 1459-1469.
Zhao D, Wang Q, Zhao Y, et al. The naturally derived small compound Osthole inhibits osteoclastogenesis to prevent ovariectomy-induced bone loss in mice. Menopause. 2018;25(12):1459-1469.
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. (2018). The naturally derived small compound Osthole inhibits osteoclastogenesis to prevent ovariectomy-induced bone loss in mice. Menopause (New York, N.Y.), 25(12), 1459-1469. https://doi.org/10.1097/GME.0000000000001150
Zhao D, et al. The Naturally Derived Small Compound Osthole Inhibits Osteoclastogenesis to Prevent Ovariectomy-induced Bone Loss in Mice. Menopause. 2018;25(12):1459-1469. PubMed PMID: 29944638.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The naturally derived small compound Osthole inhibits osteoclastogenesis to prevent ovariectomy-induced bone loss in mice. AU - Zhao,Dongfeng, AU - Wang,Qiang, AU - Zhao,Yongjian, AU - Zhang,Hao, AU - Sha,Nannan, AU - Tang,Dezhi, AU - Liu,Shufen, AU - Lu,Sheng, AU - Shi,Qi, AU - Zhang,Yan, AU - Dong,Yufeng, AU - Wang,Yongjun, AU - Shu,Bing, PY - 2018/6/27/pubmed PY - 2019/10/23/medline PY - 2018/6/27/entrez SP - 1459 EP - 1469 JF - Menopause (New York, N.Y.) JO - Menopause VL - 25 IS - 12 N2 - 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. SN - 1530-0374 UR - https://www.unboundmedicine.com/medline/citation/29944638/The_naturally_derived_small_compound_Osthole_inhibits_osteoclastogenesis_to_prevent_ovariectomy_induced_bone_loss_in_mice_ L2 - https://doi.org/10.1097/GME.0000000000001150 DB - PRIME DP - Unbound Medicine ER -