Impact of skeletal unloading on bone formation:  role of systemic and local factors.
We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH)2D3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.
Bikle
D D
DD
University of California San Francisco, Medical Service, 94121, USA.
Halloran
B P
BP
Morey-Holton
E
E
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism / Q000502:physiology; D013006:Growth Hormone; D019417:Hindlimb Suspension / Q000009:adverse effects*; D006811:Humerus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000378:metabolism*; D008297:Male; D015675:Osteocalcin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism*; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism; D018474:Weightlessness Simulation
D010281:Parathyroid Hormone; D015675:Osteocalcin; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D002117:Calcitriol; D002118:Calcium; D003345:Corticosterone