Effects of intense physical exercise on osteogenic commitment of mesenchymal progenitors

Multipotent human bone ma rrow stromal cells (hBMSCs) can dif ferentiate into osteoblasts, chondrocyte and adipocytes. MSC commitment toward a s pecif ic cell type is influenced by a multitude of stimuli and inhibitors acting on specif ic transcription factors. RUNX2, SOX9, PPARgamma2 control MSC dif ferentiation toward osteoblast, chondrocyte, adipocyte, respectively. MSCs can also be isola ted from peripheral blood [1]. Circulating MSCs represent an excellent tool for the ex vivo investigation of gene expression patterns in dif ferentiating precur sors. We have investigated how the ex pression levels of ma ster dif ferentiation genes ma y be influenced by intense physical exercise in competitive runners. Eleven ma le subjects were enrolled for collection of peripheral blood samples before and after the Run for Science 42 km ma ra thon. The samples were used to perform i) biochemical, ii) proteomic and iii) molecular analyses in order to evaluate the ef fects of intense physical exercise on bone ma ss and, in particular, on osteogenic commitment of MSC. Comparing pre­ and post­ run data we observed a 2fold increase in RUNX2 gene expression and a 2fold decrease in PPA Rga mma2 gene ex pression. Interestingly, we also observed an increased ex pression of S OX9. These preliminary data indicate how intense physica l activity eff ectively favors MSCs osteocondrogen ic commitment at the expense of the mutually exclusive adipogenic commitment. Further investigations at the molecular and biochemical level will clarif y which players trigger the observed cellular response. [1] Valenti MT et al., B one 43 (2008) 108