Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways.
Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways.
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肌肉生长抑制素通过调节 Ccdc50 基因表达和 RANKL 诱导的 NF-κB 和 MAPK 途径促进破骨细胞生成
DOI：
10.3389/fphar.2020.565163
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发表时间：
2020
影响因子：
5.6
通讯作者：
Cao L
中科院分区：
文献类型：
--
作者：
Zhi X;Chen Q;Song S;Gu Z;Wei W;Chen H;Chen X;Weng W;Zhou Q;Cui J;Cao L
肌肉生长抑制素是一种重要的细胞因子，广泛存在于骨骼肌中，对肌肉细胞的生长发育起负性调节作用。最近的研究表明，肌肉抑制素可能在骨代谢中发挥重要作用。在RAW264.7细胞和骨髓单核细胞(BMMC)中，Myostatin激活了II型受体ActRIIB的表达，我们报道了myostatin通过Ccdc50基因在体外显著促进RANKL/M-κ诱导的破骨细胞的形成，并激活了NF-MAPK B和MAPK信号通路。Myostatin的过表达促进了破骨细胞的生成和破骨细胞生成相关的标记物，包括c-Src、MMP9、CTR、CK和NFATc1。特别地，肌肉抑制素增加了Smad2的磷酸化，从而导致了NF-κB和MAPK通路的激活，从而激活了破骨细胞的形成。Ccdc50基因被鉴定为Myostatin处理后破骨细胞生成过程中表达显著降低的基因，它可以通过阻断NF-κB和MAPK信号通路来抑制Myostatin在破骨细胞生成中的作用。我们的研究表明，myostatin是一个有希望的抑制RANKL介导的破骨细胞形成的候选靶点，并可能参与骨质疏松症的治疗，而且Ccdc50基因在调节过程中发挥着重要作用。
Myostatin is a crucial cytokine that is widely present in skeletal muscle and that negatively regulates the growth and development of muscle cells. Recent research has shown that myostatin might play an essential role in bone metabolism. In RAW264.7 cells and bone marrow monocytes (BMMCs), myostatin activates the expression of the II type receptor ActR II B. Here, we report that myostatin significantly promoted RANKL/M-CSF-induced osteoclastogenesis and activated NF-κB and MAPK pathways in vitro via the Ccdc50 gene. Overexpression of myostatin promoted osteoclastogenesis and osteoclastogenesis-related markers including c-Src, MMP9, CTR, CK, and NFATc1. Specifically, myostatin increased the phosphorylation of Smad2, which led to the activation of NF-κB and MAPK pathways to activate osteoclastogenesis. Ccdc50 was identified as a gene whose expression was highly decreased in osteoclastogenesis upon myostatin treatment, and it could inhibit the function of myostatin in osteoclastogenesis by blocking NF-κB and MAPKs pathways. Our study indicates that myostatin is a promising candidate target for inhibiting RANKL-mediated osteoclastogenesis and might participate in therapy for osteoporosis, and that the Ccdc50 gene plays a significant role in the regulatory process.
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影响因子：
4.4
作者：
Bharti, AC;Takada, Y;Aggarwal, BB
通讯作者：
Aggarwal, BB
影响因子：
15.3
作者：
Asagiri, M;Sato, K;Takayanagi, H
通讯作者：
Takayanagi, H
影响因子：
82.9
作者：
Dankbar, Berno;Fennen, Michelle;Pap, Thomas
通讯作者：
Pap, Thomas
影响因子：
11.4
作者：
Farfsing, A.;Engel, F.;Pscherer, A.
通讯作者：
Pscherer, A.
DOI：
10.1002/ar.a.10044
发表时间：
2003-05-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Hamrick, MW
通讯作者：
Hamrick, MW