Ectopic expression of IGF-I and Shh by skeletal muscle inhibits disuse-mediated skeletal muscle atrophy and bone osteopenia in vivo.

Abstract

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.

• Authors: Mohammed Borhan Alzghoul, Dave Gerrard, Bruce A Watkins, Kevin Hannon
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 18 Issue 1 Pg. 221-3 (Jan 2004) ISSN: 1530-6860 [Electronic] United States
• PMID: 14597562 (Publication Type: Journal Article)

Chemical References

• Hedgehog Proteins
• Trans-Activators
• Insulin-Like Growth Factor I

Topics

• Animals
• Bone Density
• Bone Diseases, Metabolic (metabolism, pathology, therapy)
• Electroporation
• Gene Expression
• Hedgehog Proteins
• Hindlimb Suspension
• Insulin-Like Growth Factor I (genetics, metabolism)
• Mice
• Muscle Fibers, Skeletal (cytology)
• Muscle, Skeletal (metabolism)
• Muscular Atrophy
• Muscular Disorders, Atrophic (metabolism, pathology, therapy)
• Trans-Activators (genetics, metabolism)