Fig. 7. Model of BMP2-dependent osteo/chondrogenic development in mesenchymal stem cells. BMP2 predominantly determines osteo/chondrogenic development via BMPR-IA, while BMPR-IB only exerts maturing functions on osteoblast development in C3H10T1/2 cells (in preparation). Therefore, Smad1 is a signaling mediator of osteogenesis rather than of chondrogenesis (Ju et al., 2000). Osteogenesis is controlled by R-Smad-signaling during the entire osteoblast-developmental sequence, also by recruiting CBFA1 into an heteromeric complex (Hanai et al., 1999). BMP2-dependent determination of chondrogenesis in mesenchymal progenitors C3H10T1/2 seems to involve the immediate upregulation of FGFR3 by an R-Smad-independent mechanism. After this triggering event, chondrogenesis is then predominantly controlled by BMP-independent mechanisms. Therefore, FGF-mediated signaling leads to MAPK-activation and upregulation of T-box factor (Brachyury) expression that is sufficient for de novo chondrogenesis in mesenchymal progenitors C3H10T1/2. Brachyury is able to maintain FGFR3 and FGFR2 expression in an autoregulatory loop. FGFR-mediated MAPK-signaling also upregulates mRNA levels of transcription factor Sox9, which is necessary for chondrogenic development (Murakami et al., 2000).

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