Role of PTH and PTH-related peptide in skeletal development

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We published a review articule about chondrocyte differentiation using data obtained in this study(Y.Kato et al., in Tissue Enginearing for Therapeutic Use, Oshima and Ikari eds.in press). Our findings indicate that retinol-binding protein is synthesized by chondrocytes in response to PTH, PTHrp or retinoic acid, and that retinol-binding protein is involved partily in mediating the action of PTH and PTHrp on chondrocytes.We also found that PTHrp directly suppresses Indian hedgehog(Ihh)expression in chondrocytes. This action is a negative feed back mechanism to inhibit excess accumulation of PTHrP and Ihh. We also showed that PTHrp induces CEDP, a novel Rho GEF, and DEC1, a novel transcriptional factor in growth plate chondrocytes. These findings suggest that PTH and PTHrp modulate chondrocyte differentiation and bone formation via changes in retinol-binding protein, CDEP, DEC1 and Ihh.