Regulatory effects of miRNA‑181a on FasL expression in bone marrow mesenchymal stem cells and its effect on CD4+T lymphocyte apoptosis in estrogen deficiency‑induced osteoporosis

Shao,Bingyi; Fu,Xiaohui; Yu,Yang; Yang,Deqin

doi:10.3892/mmr.2018.9026

Regulatory effects of miRNA‑181a on FasL expression in bone marrow mesenchymal stem cells and its effect on CD4+T lymphocyte apoptosis in estrogen deficiency‑induced osteoporosis

Authors:
- Bingyi Shao
- Xiaohui Fu
- Yang Yu
- Deqin Yang
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Affiliations: Department of Operative Dentistry and Endodontics, Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing 401147, P.R. China, Department of Orthodontics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: May 16, 2018 https://doi.org/10.3892/mmr.2018.9026
Pages: 920-930
Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Post-menopausal osteoporosis is a bone formation disorder induced by estrogen deficiency. Estrogen deficiency facilitates the differentiation and maturation of osteoclasts by activating T lymphocytes. In our previous study, it was demonstrated that estrogen promotes bone marrow mesenchymal stem cell (BMMSC)‑induced osteoclast apoptosis through downregulation of microRNA (miR)‑181a and subsequent Fas ligand (FasL) protein accumulation. In the present study, the regulatory effects of miR‑181a on FasL expression in BMMSCs and the apoptotic effects of BMMSCs on cluster of differentiation (CD)4+T lymphocytes were investigated. An ovariectomized mouse model of osteoporosis (OVX) was established and CD4+T lymphocytes were isolated from the bones of these mice. The results demonstrated that the number of CD4+T lymphocytes was increased in the OVX group compared within the control group, thus suggesting that estrogen deficiency may increase CD4+T lymphocyte number. CD4+T lymphocytes were subsequently co‑cultured with estrogen‑treated BMMSCs, after which it was demonstrated that estrogen significantly promoted the apoptosis of CD4+T lymphocytes. Western blot analysis indicated that estrogen promoted the apoptosis of CD4+T lymphocytes through regulation of FasL expression in BMMSCs in a concentration‑dependent manner. Finally, miR‑181a was transfected into BMMSCs, which were co‑cultured with CD4+T lymphocytes in vitro and in vivo. The results revealed that miR‑181a exerted a negative regulatory effect on BMMSC‑induced CD4+T lymphocyte apoptosis by regulating FasL protein expression in BMMSCs; this maybe a key mechanism underlying the development of estrogen deficiency‑induced osteoporosis.

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