Kellum Ethan, Starr Harlan, Arounleut Phonepasong, Immel David, Fulzele Sadanand, Wenger Karl, Hamrick Mark W
Department of Orthopaedic Surgery, Medical College of Georgia, Augusta, GA 30912, USA.
Bone. 2009 Jan;44(1):17-23. doi: 10.1016/j.bone.2008.08.126. Epub 2008 Sep 13.
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-deficient (-/-) 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.
肌肉生长抑制素（GDF - 8）是骨骼肌生长的负调节因子，缺乏肌肉生长抑制素的小鼠肌肉量增加。我们之前已经表明，肌肉生长抑制素缺乏会增加整个骨骼的骨强度和生物矿化，并且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痂形态发生中的作用，我们研究了缺乏肌肉生长抑制素的小鼠的骨折愈合情况。成年野生型小鼠（+/+）、肌肉生长抑制素突变杂合子小鼠（+/-）和肌肉生长抑制素序列缺失的纯合子小鼠（-/-）在腓骨截骨术后两周和四周被纳入研究。与野生型（+/+）小鼠相比，在截骨术后两周，肌肉生长抑制素缺陷型（-/-）小鼠骨折痂中Sox - 5和BMP - 2的表达显著上调。在截骨术后两周和四周，缺乏肌肉生长抑制素的小鼠骨折痂大小显著增加，并且在截骨术后四周，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时的痂强度显著更大。我们的数据表明，肌肉生长抑制素通过抑制骨折芽基中祖细胞的募集和增殖来调节骨折痂大小。在骨折修复的早期炎症阶段，肌肉生长抑制素缺乏会增加芽基大小，最终产生具有更大骨体积和更大痂强度的骨痂。虽然肌肉生长抑制素因其对肌肉发育的影响而最为人所知，但很明显肌肉生长抑制素在骨形成和再生中也起着重要的直接作用。
