Ectopic expression of IGF-1 and Shh by skeletal muscle inhibits disuse-mediated skeletal muscle atrophy and bone osteopenia in vivo
Ectopic expression of IGF-1 and Shh by skeletal muscle inhibits disuse-mediated skeletal muscle atrophy and bone osteopenia in vivo
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DOI：
10.1096/fj.03-0293fje
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Hannon, K
中科院分区：
文献类型：
--
作者：
Alzghoul, MB;Gerrard, D;Hannon, K
在卧床休息、肢体固定和太空飞行期间失去正常的负重活动，会刺激肌肉骨骼系统的分解代谢反应，从而导致骨骼肌质量和骨矿物质的损失。肌肉和骨骼的负荷被感知并转化为控制组织形成的信号的机制仍然是肌肉骨骼研究领域的一个主要问题。在这项研究中，我们研究了两种潜在的抗萎缩蛋白，IGF-I和Shh，当电穿孔进入骨骼肌时，抑制肌肉和骨骼的废弃萎缩的能力。我们发现，在腓肠肌/比目鱼肌内，IGF-I和/或Shh的电穿孔和异位表达显著刺激肌纤维肥大和肌肉大小增加。此外，我们报道了腓肠肌/比目鱼肌内IGF-I和/或Shh的电穿孔和异位表达，减轻了在废弃性肌肉萎缩期间通常发生的肌纤维面积、肌肉质量和肌肉质量密度的损失。最后，我们发现腓肠肌/比目鱼肌内IGF-I和Shh的异位表达抑制了与后肢卸载相关的胫骨和腓骨内骨质减少的参数。这些结果支持骨骼肌可以调节骨骼维护的理论，并可能为减轻衰老，疾病和太空飞行期间的肌肉和骨骼萎缩提供潜在的新颖有效的治疗选择。
The loss of normal weight-bearing activity, which occurs during bed rest, limb immobilization, and spaceflight, stimulates a catabolic response within the musculoskeletal system, which results in a loss of skeletal muscle mass and bone mineral. The mechanism by which loading of muscle and bone is sensed and translated into signals controlling tissue formation remains a major question in the field of musculoskeletal research. In this investigation, we have examined the ability of two potentially anti-atrophic proteins, IGF-I and Shh, to inhibit disuse atrophy within muscle and bone, when electroporated into skeletal muscle. We have found that electroporation and ectopic expression of IGF-I and/or Shh within the gastrocnemius/soleus muscle significantly stimulated muscle fiber hypertrophy and increases in muscle size. In addition, we report that electroporation and ectopic expression of IGF-I and/or Shh within the gastrocnemius/soleus muscle attenuated the lost of muscle fiber area, muscle mass, and muscle mass density that normally occurs during disuse muscle atrophy. Finally, we found that ectopic expression of IGF-I and Shh within the gastrocnemius/soleus muscle inhibits parameters of osteopenia within the tibia and fibula associated with hindlimb unloading. These results support the theory that skeletal muscle can regulate bone maintenance and could offer potentially novel and efficient therapeutic options for attenuating muscle and bone atrophy during aging, illness and spaceflight.