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

ABSTRACT: Postmenopausal osteoporosis (PMO) has been recognized as an inflammatory condition. CD4+ T cells serve a key role in the interaction between bone metabolism and the immune system. Bu?Shen?Ning?Xin decoction (BSNXD), a traditional Chinese medicine, has been ultilized as a remedy for PMO. In the present study, the aim was to investigate the immune modulatory effects of BSNXD on CD4+ T cells, receptor activation of nuclear factor ?B ligand (RANKL)/osteoprotegerin (OPG) imbalance, skeletal parameters and osteoclastogenesis. Ovariectomized (OVX) mice were treated with a series of concentrations of BSNXD and then autopsied. The bone phenotype was analyzed by micro computed tomography. CD4+ T cells were isolated and their percentage was measured using flow cytometry (FCM). RANKL and OPG expression by the CD4+ T cells at the transcriptional and translational levels were quantified by reverse transcription-quantitative polymerase chain reaction, ELISA and FCM. CD4+ T cells were cultured with blood serum derived from BSNXD?treated OVX mice (BSNXD?derived serum) and the apoptosis rate was quantified by FCM. CD4+ T cells were co-cultured with bone marrow?derived macrophages and exposed to BSNXD?derived serum to whether CD4+ T cells are involved in BSNXD?modulated osteoclastogenesis and the results were quantified via tartrate?resistant acid phosphatase staining. The results revealed that BSNXD ameliorated OVX?induced bone loss, prevented the expansion of CD4+ T cells and restored the RANKL/OPG imbalance in the CD4+ T cells of OVX mice. In vitro, BSNXD?derived serum promoted the apoptosis of CD4+ T cells. The co?culture system demonstrated that CD4+ T cells from OVX mice increase osteoclastogenesis, while this effect was suppressed by BSNXD administration. The findings of the study collectively suggest that BSNXD exerts an immunoprotective effect on the bone phenotype of OVX mice by ameliorating RANKL/OPG imbalance in CD4+ T cells and attenuating osteoclastogenesis.

SUBMITTER: Zhang JL

PROVIDER: S-EPMC5979942 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Zhang Jia-Li JL Qiu Xue-Min XM Zhang Na N Tang Wei W Gober Hans-Jürgen HJ Li Da-Jin DJ Wang Ling L

International journal of molecular medicine 20180426 1

Postmenopausal osteoporosis (PMO) has been recognized as an inflammatory condition. CD4+ T cells serve a key role in the interaction between bone metabolism and the immune system. Bu‑Shen‑Ning‑Xin decoction (BSNXD), a traditional Chinese medicine, has been ultilized as a remedy for PMO. In the present study, the aim was to investigate the immune modulatory effects of BSNXD on CD4+ T cells, receptor activation of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) imbalance, skeletal parameter ...[more]

PMID: 29717766

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Project description: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.

Dataset Information

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

Publications

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

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