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The impact of skeletal unloading on bone formationSkeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During space flight bone is lost principally from the bones most loaded in the 1 g environment. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. It seems likely that matrix/cell interactions will underlie much of the mechanocoupling. Integrins are a prime mediator of such interactions. The role for systemic hormones such as PTH, GH and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs and TGF beta in modulating the cellular response to load remains unclear. Our studies demonstrate that skeletal unloading leads to resistance to the anabolic actions of IGF-I on bone as a result of failure of IGF-I to activate its own signaling pathways. This is associated with a reduction in integrin expression, suggesting crosstalk between these two pathways. As the mechanism(s) by which bone responds to changes in mechanical load with changes in bone formation is further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, and that such understanding will lead to effective treatment for disuse osteoporosis in addition to preventive measures for the bone loss that accompanies space travel.
Document ID
20040087537
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Bikle, Daniel D.
(Veterans Affairs Medical Center and University of California San Francisco, CA, United States)
Sakata, Takeshi
Halloran, Bernard P.
Date Acquired
August 21, 2013
Publication Date
June 1, 2003
Publication Information
Publication: Gravitational and space biology bulletin : publication of the American Society for Gravitational and Space Biology
Volume: 16
Issue: 2
ISSN: 1089-988X
Subject Category
Aerospace Medicine
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Musculoskeletal
Review
Non-NASA Center
Review, Tutorial

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