Pharmacological interference with transcriptional control of osteoblasts: A possible role for leptin and fatty acids in maintaining bone strength andbody lean mass

Osteoblasts pass through a sequence of events controlled by hormones and tr anscriptional factors ensuring proper development of phenotype and function al properties until the osteoblast enter the osteocyte phenotype and/or und ergo apoptosis. During its life cycle, the osteoblasts proliferate, deposit matrix proteins and mineralize it until they turn into osteocytes believed to constitute a mechanosensor mesh giving feed-back to the osteoblast to i nitiate bone modeling or remodeling necessary for the making or remaking of proper bone architecture and strength. It appears that several factors com mon to osteoblast and adipocyte differentiation determine their entry into different functional stages. Such factors are insulin, growth hormone (GH), insulin-like growth factor type I (IGF-I), transforming growth factor beta (TGF beta), platelet derived growth factor (PDGF), fibroblast growth facto r (FGF), cytokines (e.g. interleukins, interferon and tumor necrosis factor alpha (TNF alpha), bone morphogenic proteins (BMPs), glucocorticoids, reti noic acid (RA), prostaglandins and cAMP-elevating hormones. The focus of th is article is to review the effects of leptin on bone cells and bone turnov er, the peroxisome proliferator-activated receptors (PPARs) in the regulati on of bone and fat cell differentiation, hormones and fatty acids on the or chestration of osteoblast and adipocyte derived regulatory signals, and mec hanostimulation of bone on the mechanisms by which the above mentioned fact ors modulate osteoblast and adipocyte function. The hypothesis or concept i s that prescription of a certain treatment regimen to correct bone turnover , without attempting to assess how hormonal homeostasis, nutritional factor s and physical exercise may interact locally, will remain far from optimal, and may even prove detrimental to the patient's health condition.