Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice.
Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice.
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Myokine Irisin 通过 αV 整合素激活 BMP/SMAD 信号来促进成骨，并调节小鼠骨量
DOI：
10.7150/ijbs.63505
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发表时间：
2022
影响因子：
9.2
通讯作者：
Rui Y
中科院分区：
文献类型：
--
作者：
Xue Y;Hu S;Chen C;He J;Sun J;Jin Y;Zhang Y;Zhu G;Shi Q;Rui Y
鸢尾素因其双向调控骨生成和破骨细胞生成而被认为有助于骨稳态。然而，鸢尾素参与间充质干细胞/基质细胞（MSCs）衍生成骨的机制仍在研究中。纤维连接蛋白III型结构域蛋白5 （FNDC5）是鸢尾素的前体蛋白，与野生型（WT）窝鼠相比，FNDC5-/-小鼠骨量明显减少，共同表现为骨密度（BMD）降低，骨形成受损，血清I型前胶原（P1NP） n端特性降低。同时，FNDC5-/-小鼠骨吸收增强，伴有酒石酸磷酸酶（TRAP）染色细胞形态学和血清中1型胶原交联c -端肽（CTX）水平升高。体外研究表明，鸢尾素的缺乏阻碍了FNDC5-/-小鼠的msc来源的成骨。鸢尾素的加入通过激活αV整合素诱导的ERK/STAT通路，进而增强骨形态发生蛋白2 （bone morphogenetic protein 2, BMP2）表达和BMP/SMAD信号激活，促进WT和缺乏鸢尾素的MSCs成骨。综上所述，这些发现进一步表明鸢尾素调节骨稳态。此外，鸢尾素通过与αV整合素结合并激活BMP/SMAD信号传导从而促进msc来源的成骨。因此，鸢尾素可能是治疗骨质疏松和骨缺损的一个有前景的靶点。
Irisin is well-known to contribute to bone homeostasis due to its bidirectional regulation on osteogenesis and osteoclastogenesis. However, the mechanisms of irisin involved in mesenchymal stem/stromal cells (MSCs)-derived osteogenesis are still under investigated. Fibronectin type III domain-containing protein 5 (FNDC5) is the precursor protein of irisin, compare with wild type (WT) littermates, FNDC5-/- mice lost bone mass significantly, collectively evidenced by the decrease of bone mineral density (BMD), impaired bone formation and reduced N-terminal propertied of type I procollagen (P1NP) in sera. Meanwhile, the bone resorbing of FNDC5-/- mice has enhanced accompanied by increased tartrate phosphatase (TRAP) staining cells morphologically and cross-Linked C-telopeptide of type 1 collagen (CTX) level in sera. In vitro study showed that lack of irisin impeded the MSC-derived osteogenesis of FNDC5-/- mice. The addition of irisin promote the osteogenesis of WT and irisin-deficient MSCs, by activating αV integrin-induced ERK/STAT pathway, subsequently enhancing bone morphogenetic protein 2 (BMP2) expression and BMP/SMAD signaling activation. Taken together, these findings further indicate that irisin regulates bone homeostasis. Moreover, irisin promotes MSC-derived osteogenesis by binding to αV integrin and activating BMP/SMAD signaling consequently. Thus, irisin may be a promising therapeutic target for osteoporosis and bone defects.
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影响因子：
12.4
作者：
Chen Q;Shou P;Zheng C;Jiang M;Cao G;Yang Q;Cao J;Xie N;Velletri T;Zhang X;Xu C;Zhang L;Yang H;Hou J;Wang Y;Shi Y
通讯作者：
Shi Y
影响因子：
64.5
作者：
Antebi YE;Linton JM;Klumpe H;Bintu B;Gong M;Su C;McCardell R;Elowitz MB
通讯作者：
Elowitz MB
影响因子：
3.9
作者：
Forouzanfar, Mahboobeh;Rabiee, Farzaneh;Nasr-Esfahani, Mohammad Hossein
通讯作者：
Nasr-Esfahani, Mohammad Hossein
影响因子：
64.5
作者：
Kim, Hyeonwoo;Wrann, Christiane D.;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
4.5
作者：
Chen P;Li Z;Hu Y
通讯作者：
Hu Y