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Throughout life, a balance exists within the marrow cavity between adipose tissue and bone. Each tissue derives from a common progenitor cell known both as a 'bone marrow-derived multipotent stromal cell' and as a 'mesenchymal stem cell' (BMSC). The majority of in vitro and in vivo data suggest that BMSCs differentiate into adipocytes or osteoblasts in a reciprocal manner. For example, while ligand induction of the transcription factors peroxisome proliferator-activated receptor γ initiates BMSC adipogenesis, it suppresses osteogenesis. Nevertheless, this hypothesis may oversimplify a complex regulatory paradigm. The picture may be further complicated by the systemic impact of extramedullary adipose depots on bone via the secretion of protein adipokines and lipid metabolites. This review focuses on past and current literature examining the mechanisms governing the adipose-bone interface. [ABSTRACT FROM AUTHOR]

Osterix (Osx), a BMP-2-regulated transcription factor, controls expression of genes essential for osteoblast differentiation. Using progressive deletion of the Osx promoter, we characterized a Smad binding element (SBE) between -552 and -839 bp from its transcription start site. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed binding and in vivo recruitment of Smads 1 and 5 to the Osx SBE. Inactivation of PI 3-kinase by the pharmacologic inhibitor Ly294002 or by dominant negative (DN) enzyme significantly blocked BMP-2-induced Osx protein and mRNA expression and Osx transcription. Finally, both DN PI 3-kinase and DN Akt significantly attenuated Smad 5-dependent transcription of Osx, demonstrating the first evidence for a concerted action of PI 3-kinase/Akt signaling with BMP-specific Smads for expression of Osx. [ABSTRACT FROM AUTHOR]