Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume.
Myostatin (GDF-8) deficiency increases fracture callus size, Sox-5 expression, and callus bone volume.
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Myostatin（GDF-8）缺乏会增加断裂的愈伤组织大小，SOX-5表达和愈伤组织骨体积。
DOI：
10.1016/j.bone.2008.08.126
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发表时间：
2009-01
期刊：
影响因子：
4.1
通讯作者：
Hamrick, Mark W.
中科院分区：
文献类型：
--
作者：
Kellum, Ethan;Starr, Harlan;Arounleut, Phonepasong;Immel, David;Fulzele, Sadanand;Wenger, Karl;Hamrick, Mark W.
肌生长抑制素（GDF-8）是骨骼肌生长的负调节因子，缺乏肌生长抑制素的小鼠肌肉质量增加。我们之前的研究表明，肌肉生长抑制素缺乏会增加骨骼强度和整个骨骼的生物矿化，而其他人已经证明，肌肉生长抑制素在骨折修复的最早阶段表达。为了确定肌肉生长抑制素在骨折愈伤组织形态发生中的作用，我们研究了缺乏肌肉生长抑制素的小鼠骨折愈合。成年野生型小鼠（+/+）、肌肉生长抑制素突变杂合的小鼠（+/−）和肌肉生长抑制素序列中断纯合的小鼠（−/−）在腓骨截骨后2周和4周进行研究。在断骨2周后，与野生型（+/+）小鼠相比，肌生成抑制素缺乏（- / -）小鼠骨折骨痂中Sox-5和BMP-2的表达显著上调。在截骨后2周和4周，缺乏肌肉生长抑制素的小鼠骨折骨痂大小显著增加，在截骨后4周，与肌肉生长抑制素+/+小鼠相比，肌肉生长抑制素- / -小鼠的总骨组织面积和三点弯曲的骨痂强度显著增加。我们的数据表明，肌生长抑制素通过抑制骨折胚泡中祖细胞的募集和增殖来调节骨折愈伤组织的大小。在骨折修复的早期炎症阶段，肌生长抑制素缺乏会增加胚泡大小，最终产生骨体积更大、强度更大的骨化骨痂。虽然肌肉生长抑制素对肌肉发育的影响最为人所知，但也很清楚，肌肉生长抑制素在骨形成和再生中起着重要而直接的作用。
Myostatin (GDF-8) is a negative regulator of skeletal muscle growth and mice lacking myostatin show increased muscle mass. We have previously shown that myostatin deficiency increases bone strength and biomineralization throughout the skeleton, and others have demonstrated that myostatin is expressed during the earliest phase of fracture repair. In order to determine the role of myostatin in fracture callus morphogenesis, we studied fracture healing in mice lacking myostatin. Adult wild-type mice (+/+), mice heterozygous for the myostatin mutation (+/−), and mice homozygous for the disrupted myostatin sequence (−/−) were included for study at two- and four-weeks following osteotomy of the fibula. Expression of Sox-5 and BMP-2 were significantly upregulated in the fracture callus of myostatin-deficent (−/−) mice compared to wild-type (+/+) mice at two-weeks following osteotomy. Fracture callus size was significantly increased in mice lacking myostatin at both two- and four-weeks following osteotomy, and total osseous tissue area and callus strength in three-point bending were significantly greater in myostatin −/− mice compared to myostatin +/+ mice at four weeks post-osteotomy. Our data suggest that myostatin functions to regulate fracture callus size by inhibiting the recruitment and proliferation of progenitor cells in the fracture blastema. Myostatin deficiency increases blastema size during the early inflammatory phase of fracture repair, ultimately producing an ossified callus having greater bone volume and greater callus strength. While myostatin is most well known for its effects on muscle development, it is also clear that myostatin plays a significant, direct role in bone formation and regeneration.
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影响因子：
2.8
作者：
Hamrick, MW;Pennington, C;Byron, CD
通讯作者：
Byron, CD
影响因子：
4.8
作者：
Artaza, JN;Bhasin, S;Gonzalez-Cadavid, NF
通讯作者：
Gonzalez-Cadavid, NF
影响因子：
6.2
作者：
Gerstenfeld, LC;Wronski, TJ;Einhorn, TA
通讯作者：
Einhorn, TA
DOI：
10.1073/pnas.0408729102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Wagner, KR;Liu, XS;Allen, RE
通讯作者：
Allen, RE
影响因子：
56.9
作者：
Zimmers, TA;Davies, MV;Lee, SJ
通讯作者：
Lee, SJ