Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro
Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro
复制标题
体外保护骨素通过 AMPK/mTOR/p70S6K 信号通路增强自噬，抑制破骨细胞分化和骨吸收。
DOI：
10.1002/jcb.27468
复制
发表时间：
2019-02-01
影响因子：
4
通讯作者：
Liu, Zongping
中科院分区：
文献类型：
--
作者：
Tong, Xishuai;Gu, Jianhong;Liu, Zongping
破骨细胞是由造血干细胞融合形成的高度分化的终末细胞。此前，骨保护素（osteoprotegerin， OPG）通过阻断核因子b配体受体激活因子（receptor activator of nuclear factor-B ligand， RANKL）结合RANK间接机制抑制破骨细胞分化和骨吸收。此外，自噬在破骨细胞的分化和功能中起着重要作用。然而，自噬是否参与opg抑制破骨细胞形成和骨吸收尚不清楚。为了阐明自噬在opg抑制破骨细胞分化和骨吸收中的作用，我们使用诱导M-CSF和RANKL的小鼠骨髓单核/巨噬细胞（BMM）的原代破骨细胞。结果显示，自噬相关蛋白表达上调；抗酒石酸酸性磷酸酶阳性破骨细胞数量和骨吸收活性降低；LC3点和自噬体数量增加，激活AMPK/mTOR/p70S6K信号通路。此外，氯喹（作为自噬/溶酶体抑制剂，CQ）或雷帕霉素（作为自噬/溶酶体抑制剂，Rap）通过AMPK/mTOR/p70S6K信号通路减弱OPG对破骨细胞的分化和骨吸收活性。我们的数据表明，自噬在体外通过AMPK/mTOR/p70S6K信号通路抑制OPG破骨细胞分化和骨吸收中起关键作用。
Osteoclasts are highly differentiated terminal cells formed by fusion of hematopoietic stem cells. Previously, osteoprotegerin (OPG) inhibit osteoclast differentiation and bone resorption by blocking receptor activator of nuclear factor-B ligand (RANKL) binding to RANK indirect mechanism. Furthermore, autophagy plays an important role during osteoclast differentiation and function. However, whether autophagy is involved in OPG-inhibited osteoclast formation and bone resorption is not known. To elucidate the role of autophagy in OPG-inhibited osteoclast differentiation and bone resorption, we used primary osteoclast derived from mice bone marrow monocytes/macrophages (BMM) by induced M-CSF and RANKL. The results showed that autophagy-related proteins expression were upregulated; tartrate-resistant acid phosphatase-positive osteoclast number and bone resorption activity were decreased; LC3 puncta and autophagosomes number were increased and activated AMPK/mTOR/p70S6K signaling pathway. In addition, chloroquine (as the autophagy/lysosome inhibitor, CQ) or rapamycin (as the autophagy/lysosome inhibitor, Rap) attenuated osteoclast differentiation and bone resorption activity by OPG treatment via AMPK/mTOR/p70S6K signaling pathway. Our data demonstrated that autophagy plays a critical role in OPG inhibiting osteoclast differentiation and bone resorption via AMPK/mTOR/p70S6K signaling pathway in vitro.