Increased bone mineral density in the femora of GDF8 knockout mice
Increased bone mineral density in the femora of GDF8 knockout mice
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DOI：
10.1002/ar.a.10044
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发表时间：
2003-05-01
期刊：
影响因子：
--
通讯作者：
Hamrick, MW
中科院分区：
文献类型：
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作者：
Hamrick, MW
GDF8（肌生长抑制素）是分泌性生长和分化因子转化生长因子 (TGF)-β 超家族的成员，是骨骼肌生长的负调节因子。 GDF8 敲除小鼠的骨骼肌质量大约是正常小鼠的两倍。通过检查雌性 GDF8 敲除小鼠股骨中的骨矿物质含量 (BMC) 和骨矿物质密度 (BMD)，研究了肌肉质量增加对骨建模的影响。双能X射线骨密度测定法（DEXA）密度测定法用于测量全股骨BMC和BMD，pQCT密度测定法用于从两个不同位置（中干和远端干骺端）截取的横截面计算BMC和BMD。 DEXA结果显示，基因敲除小鼠的股骨骨密度显着高于正常小鼠。外周定量计算机断层扫描 (pQCT) 数据表明，GDF8 敲除小鼠的中轴皮质 BMC 增加约 10% (P = .01)，干骺端皮质 BMC 增加超过 20% (P < .001)。同样，敲除显示两个位置的皮质厚度增加了约 10% (P < .001)，并且皮质 BMD 显着增加 (P < .001)。这些结果表明 GDF8 功能的抑制剂可能是增加肌肉质量和 BMD 的有用药物。 (C) 2003 Wiley-Liss, Inc.
GDF8 (myostatin), a member of the transforming growth factor (TGF)-beta superfamily of secreted growth and differentiation factors, is a negative regulator of skeletal muscle growth. GDF8 knockout mice have approximately twice the skeletal muscle mass of normal mice. The effects of increased muscle mass on bone modeling were investigated by examining bone mineral content (BMC) and bone mineral density (BMD) in the femora of female GDF8 knockout mice. Dual-energy X-ray absorptiometry (DEXA) densitometry was used to measure whole-femur BMC and BMD, and pQCT densitometry was used to calculate BMC and BMD from cross-sections taken at two different locations: the midshaft and the distal metaphysis. The DEXA results show that the knockout mice have significantly greater femoral BMD than normal mice. The peripheral quantitative computed tomography (pQCT) data indicate that the GDF8 knockout mice have approximately 10% greater cortical BMC (P = .01) at the midshaft and over 20% greater cortical BMC at the metaphysis (P < .001). Likewise, knockouts show approximately 10% greater cortical thickness (P < .001) and significantly greater cortical BMD (P < .001) at both locations. These results suggest that inhibitors of GDF8 function may be useful pharmacological agents for increasing both muscle mass and BMD. (C) 2003 Wiley-Liss, Inc.