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

摘要

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 (Fast) 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 CD47 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.