RAR and BMP signalling in chondrogenesis

As mentioned earlier, the BMPs play a prominent role in skeletogenesis and are important at several stages during the chondrogenic process. Inhibition of BMP signalling leads to a number of skeletal defects, some of which overlap with the defects observed in the aforementioned RARa transgenic animals. Furthermore, several reports have shown that RAR signalling can modify and/or directly regulate the expression of BMPs (Heller et al 1999). Northern blot analyses and whole-mount in situ hybridization studies, however, reveal no dramatic differences in Brnp2 or 4 expression between wild-type and transgenic mice. To directly assess the contribution of BMP signalling to the transgenic phenotype, we examined the ability of BMPs to rescue cartilage formation in transgenic cultures. Treatment of transgenic cultures with either BMP2 or 4 stimulates cartilage nodule formation, but fails to induce differentiation of transgene-expressing cells into chondroblasts. Instead, both molecules promote condensation of transgene-expressing cells. Treatment of wild-type micromass cultures with Noggin (an inhibitor of BMP2 and 4) suppresses cartilage formation, but the addition of an RARa antagonist to these Noggin-treated cultures can restore nodule formation (Weston et al 2000). Taken together, these results suggest that RA signalling functions downstream of a BMP-mediated signal to regulate chondroblast differentiation.

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