FAM5C is a soluble osteoblast differentiation factor linking muscle to bone
FAM5C is a soluble osteoblast differentiation factor linking muscle to bone
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DOI：
10.1016/j.bbrc.2011.12.147
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发表时间：
2012-02-03
影响因子：
3.1
通讯作者：
Kaji, Hiroshi
中科院分区：
文献类型：
--
作者：
Tanaka, Ken-ichiro;Matsumoto, Erika;Kaji, Hiroshi
肌肉质量与更高的骨量和骨折风险的降低有关。然而，肌肉组织和骨代谢之间的相互作用尚不完全清楚，可能存在一些在肌肉组织中产生的具有骨合成代谢活性的体液因子。因此，我们研究了FAM5C在成骨细胞分化和肌肉与骨之间的相互作用中的作用。SiRNA下调内源性FAM5C后，成骨细胞MC3T3-E1和小鼠颅骨成骨细胞中Osterix、碱性磷酸酶(ALP)和骨钙素(OCN)的表达水平以及I型胶原和B-catenin的表达水平均降低，而FAM5C的过表达可显著拮抗Osterix的表达。骨形态发生蛋白-2诱导C2C12细胞碱性磷酸酶和骨钙素基因的表达FAM5C过表达和β抑制的C2C12细胞的条件培养液分别增加和降低MC3T3-E1细胞Osterix、ALP和OCN的mRNA水平。综上所述，本研究首次表明FAM5C促进分化成骨细胞分化，FAM5C调节的成肌细胞条件培养液的作用与FAM5C对成骨细胞表型的影响呈正相关。FAM5C可能是肌肉细胞产生的一种重要的体液骨合成因子。(C)2012 Elsevier Inc.保留所有权利。
Muscle mass is related to higher bone mass and a reduction in fracture risk. However, the interactions between muscle tissues and bone metabolism are incompletely understood and there might be some humoral factors that are produced in muscle tissues and exhibit bone anabolic activity. We therefore investigated the role of FAM5C in osteoblast differentiation and the interactions between muscle and bone. A reduction of endogenous FAM5C by siRNA reduced the levels of osterix, alkaline phosphatase (ALP) and osteocalcin (OCN) mRNA as well as the levels of type 1 collagen and B-catenin in mouse osteoblastic MC3T3-E1 cells and mouse calvarial osteoblasts, although FAM5C overexpression significantly antagonized the levels of osterix. ALP and OCN mRNA induced by bone morphogenetic protein-2 in C2C12 cells. The conditioned medium from FAM5C-overexpressed and beta-suppressed C2C12 cells increased and decreased the levels of osterix, ALP and OCN mRNA in MC3T3-E1 cells, respectively. In conclusion, the present study is the first to show that FAM5C enhances osteoblast differentiation in differentiated osteoblasts, and that the effects of the conditioned medium from FAM5C-modulated myoblastic cells were positively correlated with the effects of FAM5C on osteoblast phenotype in osteoblasts. FAM5C might be an important humoral bone anabolic factor produced from muscle cells. (C) 2012 Elsevier Inc. All rights reserved.