The Skeletal Subsystem as an Integrative Physiology Paradigm

Homeostatic bone remodeling depends on precise regulation of osteoblast-osteoclast coupling through intricate endocrine, immune, neuronal, and mechanical factors. The osteoblast-osteoclast model of bone physiology with layers of regulatory complexity can be investigated as a component of a local ske...

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Bibliographic Details
Published in:Current osteoporosis reports 2010-12, Vol.8 (4), p.168-177
Main Authors: Weiss, Aaron J., Iqbal, Jameel, Zaidi, Neeha, Mechanick, Jeffrey I.
Format: Article
Language:English
Subjects:
Adipose Tissue - physiology
Animals
Bone Remodeling - physiology
Bone Resorption - physiopathology
Cytokines - physiology
Epidemiology
Homeostasis - physiology
Humans
Medicine
Medicine & Public Health
Orthopedics
Osteoblasts - physiology
Osteoclasts - physiology
Osteocytes - physiology
Parathyroid Hormone - physiology
RANK Ligand - physiology
Thyrotropin - physiology
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Summary:Homeostatic bone remodeling depends on precise regulation of osteoblast-osteoclast coupling through intricate endocrine, immune, neuronal, and mechanical factors. The osteoblast-osteoclast model of bone physiology with layers of regulatory complexity can be investigated as a component of a local skeletal subsystem or as a part of a complete whole-body system. In this review, we flip the traditional investigative paradigm of scientific experimentation (“bottom–top research”) to a “top–bottom” approach using systems biology. We first establish the intricacies of the two-cell model at the molecular signaling level. We then provide, on a systems level, an integrative physiologic approach involving many recognized organ-level subsystems having direct and/or indirect effects on bone remodeling. Lastly, a hypothetical model of bone remodeling based on frequency and amplitude regulatory mechanisms is presented. It is hoped that by providing a thorough model of skeletal homeostasis, future progress can be made in researching and treating skeletal morbidities.
ISSN:1544-1873
1544-2241
DOI:10.1007/s11914-010-0033-0