Molecular regulation of mesenchymal stem cell cytodifferentiation programs. Extracellular molecular signaling and mechanical inducers of differentiation transduce effects through putative receptors, channels, and/or other cell-surface-associated mechanisms. Downstream crosstalk of signaling pathways, including that between distinct mitogen-activated protein kinases (MAPKs) and R-Smads, provides a level of specificity that gives rise to unique lineages, such as chondrocytes and osteoblasts. Specificity of lineage differentiation can also result from the recruitment of master transcriptional switches with binary regulation of cell fate, such as TAZ (transcriptional coactivator with PDZ-binding motif). Depending on potentially unique multiprotein complexes that it may form in response to specific upstream signaling, TAZ promotes osteogenesis and inhibits adipogenesis. Furthermore, coregulator subtypes can be invoked, such as tension-induced/-inhibited proteins (TIPs), which regulate adipogenesis and myogenesis. Specific molecular induction/regulation of cardiomyogenic and tenogenic-specific development are as yet largely unknown, with the exception of those depicted. Broken lines, unknown or putative; solid lines, as in published data; *, juxtaposing cell; GDF, growth and differentiation factor; TGF, transforming growth factor; BMP, bone morphogenetic protein; FA, fatty acid; βcat, β-catenin; PPAR, peroxisome proliferator-activated receptor; MSK, mitogen- and stress-activated protein kinase; PCAF, p300/CBP-associated factor; Ac, acetyl; c, chondroblast; o, osteoblast; a, adipoblast; m, myoblast; cm, cardiomyoblast; t, tenoblast.
Kolf et al. Arthritis Research & Therapy 2007 9:204 doi:10.1186/ar2116