Figure 3

Multiple factors control MSC differentiation. The lineage commitment of MSCs can be regulated by three major cues, including chemical, physical, and biological factors. Chemical factors have been proven to be important in directing adipogenesis and osteogenesis of MSCs in vitro through regulating key transcription factors during MSC differentiation. In vivo, the differentiation of MSCs can also be altered by physical factors in the stem cell niche. Investigations into the regulation of MSC differentiation commitment by cell shape, external mechanical forces, extracellular matrix or geometric structures have provided very useful information for stem cell-based bone tissue regeneration/engineering. Meanwhile, tilted differentiation balance of MSCs is also observed during aging or other pathological processes, arguing for the roles of biological factors in lineage commitment of MSCs. Taken together, these three types of factors likely work closely and cooperate with each other to regulate MSC differentiation. IBMX, isobutylmethylxanthine; βGP, β-glycerophosphate