Bu-Shen-Ning-Xin decoction: inhibition of osteoclastogenesis by abrogation of the RANKL-induced NFATcl and NF-κB signaling pathways via selective estrogen receptor α
Introduction: Bu-Shen-Ning-Xin decoction (BSNXD) is a traditional Chinese medicinal composition that has been used as a remedy for postmenopausal osteoporosis, but the mechanisms affecting bone metabolism are not fully understood. Purpose: We investigated the molecular mechanism and signaling pathwa...
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Published in | Drug design, development and therapy p. 3755 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Dove Medical Press Limited
01.01.2015
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Subjects | |
Online Access | Get full text |
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Summary: | Introduction: Bu-Shen-Ning-Xin decoction (BSNXD) is a traditional Chinese medicinal composition that has been used as a remedy for postmenopausal osteoporosis, but the mechanisms affecting bone metabolism are not fully understood. Purpose: We investigated the molecular mechanism and signaling pathway underlying the effect of BSNXD on osteoclastogenesis. Materials and methods: A postmenopausal osteoporosis animal model generated by ovariectomy was administered BSNXD and drug-derived serum was prepared. An enzyme immunoassay was conducted to measure the 17-β-estradiol (E2) concentration in the drug-derived serum. Bone marrow-derived monocyte/macrophage precursor cells were treated with drug-derived serum, and tartrate-resistance acid phosphatase staining was conducted to observe osteoclastogenesis. A bone resorption assay was performed to analyze the effect on osteoclastic resorptive function. Real-time PCR, flow cytometry, Western blotting, transfection, and luciferase assays were conducted to explore the related mechanism. Results: E2 was not elevated in BSNXD-derived serum. BSNXD-derived serum suppressed receptor activation of nuclear factor kB ligand (RANKL)-activated osteoclastogenesis in a dose-dependent manner; this effect could be reversed by estrogen receptor a antagonist methyl-piperidino-pyrazole. The serum suppressed RANKL-induced NF-κB transcription and inhibited the accumulation of nuclear factor of activated T-cells, cytoplasmic 1 in osteoclast precursor cells; the inhibitory effect was abolished by methyl-piperidino-pyrazole but not the estrogen receptor P antagonist or androgen receptor antagonist. Conclusion: These results collectively suggest that administration of BSNXD presents inhibitory effects on osteoclast differentiation by abrogating the RANKL-induced nuclear factor of activated T-cells, cytoplasmic 1 and NF-κB signaling pathways downstream of estrogen receptor a, thereby contributing to the inhibitory effect on bone resorption. Keywords: herbal formula, osteoclastogenesis, estrogen receptor α, NF-κB, NFATc1 |
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ISSN: | 1177-8881 1177-8881 |
DOI: | 10.2147/DDDT.S88512 |