MODEL-BASED ANALYSIS OF IGF-1 EFFECT ON OSTEOBLAST AND OSTEOCLAST REGULATION IN BONE TURNOVER
| Autor: | Wang-Hee Lee, Martin R. Okos |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Ecology biology Activator (genetics) Chemistry Applied Mathematics Regulator 030209 endocrinology & metabolism Osteoblast General Medicine Agricultural and Biological Sciences (miscellaneous) Bone remodeling 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology medicine.anatomical_structure Osteoclast RANKL Internal medicine Bone cell medicine biology.protein Receptor |
| Zdroj: | Journal of Biological Systems. 24:63-89 |
| ISSN: | 1793-6470 0218-3390 |
| Popis: | The main determinant of bone Ca accretion is a bimolecular regulatory network on osteoblast (OB) and osteoclast (OC). Even though IGF-1 is known as an important regulator in bone cell cycle, little has been done to model IGF-1 action in bone cell regulation. Thus, the objective is to develop a mathematical model that depicts the regulatory action of IGF-1 onto the OB and OC interaction, and to evaluate adolescent and adult bone Ca accretion in response to differences in IGF-1 levels. As a result, a dynamic model of OB and OC with two main regulatory systems, i.e., Receptor Activator for Nuclear Factor [Formula: see text]B (RANK)-RANK Ligand (RANKL)-osteoprogerin (OPG) system, and TGF-[Formula: see text], was augmented with the IGF-1, and incorporated into Ca kinetic data to predict exchangeable bone Ca. The developed model could predict a change in OB and OC levels in response to perturbations in regulators, producing results consistent with bone physiology and published experimental data. The model also estimated parametric difference in regulators between adults and adolescents, suggesting that RANKL/OPG in adolescents was about 4 times higher than in adults, while adolescent serum PTH and IGF-1 concentrations were 60% and 220% of those of adults, respectively. This study highlighted the influence of IGF-1 on the regulation of bone cells in positively modulating bone Ca, suggesting that IGF-1 may be an effective target for reducing bone loss by promoting mature OB. |
| Databáze: | OpenAIRE |
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