Abstract
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.
Original language | English (US) |
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Pages (from-to) | 168-177 |
Number of pages | 10 |
Journal | Current Osteoporosis Reports |
Volume | 8 |
Issue number | 4 |
DOIs | |
State | Published - Dec 2010 |
Externally published | Yes |
Keywords
- Bone remodeling
- Immune system
- Integrative physiology
- Osteoblast
- Osteoclast
- Osteocyte
- Systems biology
- Vitamin D
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism