Bu-Shen-Ning-Xin decoction: inhibition of osteoclastogenesis by abrogation of the RANKL-induced NFATc1 and NF-κB signaling pathways via selective estrogen receptor α

Abstract

IntroductionBu-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.PurposeWe investigated the molecular mechanism and signaling pathway underlying the effect of BSNXD on osteoclastogenesis.Materials and methodsA 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.ResultsE2 was not elevated in BSNXD-derived serum. BSNXD-derived serum suppressed receptor activation of nuclear factor κB ligand (RANKL)-activated osteoclastogenesis in a dose-dependent manner; this effect could be reversed by estrogen receptor α 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 β antagonist or androgen receptor antagonist.ConclusionThese 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 α, thereby contributing to the inhibitory effect on bone resorption.

Bu-Shen-Ning-Xin Decoction ameliorated the osteoporotic phenotype of ovariectomized mice without affecting the serum estrogen concentration or uterus

“…Our results showed that BSNXD inhibited osteoclastogenesis by abrogation of the RANKL-induced NFATc1 and NF-κB signaling pathways via selective estrogen receptor α. 41 …”

Bu‑Shen‑Ning‑Xin decoction suppresses osteoclastogenesis by modulating RANKL/OPG imbalance in the CD4+ T lymphocytes of ovariectomized mice

“…These products were made with good manufacturing practice at the Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College. The eight crude herbs powder of BSNXD was prepared according to the Chinese Pharmacopoeia 2005 ( 34 , 35 ). Crude water extracts were prepared from powdered BSNXD ( 34 , 35 ).…”

“…The eight crude herbs powder of BSNXD was prepared according to the Chinese Pharmacopoeia 2005 ( 34 , 35 ). Crude water extracts were prepared from powdered BSNXD ( 34 , 35 ). The fingerprint analysis of BSNXD has been conducted previously in a previous study ( 30 ).…”

Iridoid Glycosides From Morinda Officinalis F. C. How Alleviate Rheumatoid Arthritis and Its Associated Bone Deterioration and Protect Against Methotrexate-induced Toxicity in Collagen-induced Arthritic Rats

“…It was found in our study that MOIG markedly inhibited the activation of NF-κB of OCs, decreased the expression of NFATC1and C-Fos, curbed the expression of OCrelated genes such as MMP9 and CtsK. In the process of OC differentiation and maturation, it can accumulate TRAF6 and activate downstream signaling pathways like NF-κB, JNK and p38 [49]. Studies demonstrated that NF-κB knockout mice developed osteopetrosis due to the decreased expression of OCs [50], suggesting that MOIG could inhibit the degradation of IκBα and phosphorylation of P65.…”