Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.
Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.
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DOI：
10.1007/s00198-015-3226-7
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Phillips CL
中科院分区：
文献类型：
--
作者：
Oestreich AK;Carleton SM;Yao X;Gentry BA;Raw CE;Brown M;Pfeiffer FM;Wang Y;Phillips CL
患有成骨不全症（+/oim）（一种骨脆性疾病）的小鼠与肌肉过度生长的小鼠进行交配，以测试通过基因增加肌肉质量是否会改善骨骼质量和强度。结果表明，携带这两种突变的小鼠的股骨比它们的+/oim 同窝小鼠具有更好的机械完整性。成骨不全症是一种遗传性结缔组织疾病，主要是由于 I 型胶原基因突变导致骨骼畸形和脆弱。目前，尚无治愈方法，治疗策略包括使用抗骨吸收药物和手术支具，但成功率有限，而且潜在的不良反应很大。骨骼是一种机械传感器官，可以通过增加新骨形成和改变骨骼几何形状以承受增加的力来响应高机械负载。骨骼肌是骨骼生理负荷的主要来源，骨骼强度与肌肉质量成正比。为了验证成骨不全小鼠模型小鼠 (oim) 肌肉质量的同源性增加将改善其受损的骨质量和强度这一假设，将杂合 (+/oim) 小鼠与缺乏肌肉生长抑制素 (+/mstn)（肌肉生长的负调节因子）的小鼠交配。对所得成年后代的后肢肌肉质量、骨微结构、生理化学和生物力学完整性进行了评估。生成了缺乏肌生长抑制素（+/mstn +/oim）的+/oim小鼠，并证明与+/oim小鼠相比，肌生长抑制素缺乏增加了+/mstn +/oim小鼠的体重、肌肉质量和生物力学强度。此外，肌生长抑制素缺乏改变了+/oim骨的理化特性，但没有改变骨重塑。肌生长抑制素缺乏通过增加肌肉质量并同时改善骨微结构和理化特性，部分改善了成年+/oim小鼠股骨生物力学强度降低的情况。
Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.
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在主要成骨的鼠模型中，成骨细胞生成受损：成骨的新靶标不完美的药物治疗。
影响因子：
5.2
作者：
Gioia, Roberta;Panaroni, Cristina;Besio, Roberta;Palladini, Giovanni;Merlini, Giampaolo;Giansanti, Vincenzo;Scovassi, Ivana A.;Villani, Simona;Villa, Isabella;Villa, Anna;Vezzoni, Paolo;Tenni, Ruggero;Rossi, Antonio;Marini, Joan C.;Forlino, Antonella
通讯作者：
Forlino, Antonella
影响因子：
3.2
作者：
Elkasrawy, Moataz;Immel, David;Hamrick, Mark W.
通讯作者：
Hamrick, Mark W.
DOI：
10.1097/ta.0b013e3181c451f4
发表时间：
2010-09
期刊：
The Journal of trauma
影响因子：
--
作者：
Hamrick MW;Arounleut P;Kellum E;Cain M;Immel D;Liang LF
通讯作者：
Liang LF
影响因子：
1.2
作者：
Hosaka, Yoshinao Z.;Ishibashi, Mika;Nishimura, Takanori
通讯作者：
Nishimura, Takanori
影响因子：
4.8
作者：
Li, Zhao Bo;Kollias, Helen D.;Wagner, Kathryn R.
通讯作者：
Wagner, Kathryn R.