Evidence that the Protein Tyrosine Phosphatase (PC12,Br7,Si) Gamma (-) isoform modulates chondrogenic patterning and growth

One of the earliest events in bone morphogenesis is the condensation of emb ryonic mesenchymal cells into chondroblasts and their subsequent proliferat ion and differentiation into chondrocytes. During this time, certain signal ing cascades operate to establish proper patterning and differentiation of the cartilaginous skeleton. Characterization of the signaling pathways invo lved in these processes remains to be accomplished. We have identified a no vel murine cytosolic tyrosine phosphatase termed PTPPBS gamma (+/-) which i s a member of the PTP PC12,Br7,SI (PTPPBS) family. Spatiao-temporal express ion analysis of the members of this tyrosine phosphatase family demonstrate s significant expression of the gamma (-) splice variant in the cartilagino us skeleton. Using an embryonic mandibular explant culture system to serve as a model for cartilage formation, we examined the potential roles of the PTPPBS gamma phosphatase by loss-of-function studies achieved with antisens e oligodeoxynucleotides. These studies demonstrated that loss of expression of the PTPPBS gamma (-) isoform resulted in abnormal patterning of Meckel' s cartilage and an increase in the size of the chondrogenic regions. In gam ma antisense-treated explants, bromodeoxyuridine-pulse labeling studies rev ealed increased proliferation of chondroblasts bordering along precartilagi nous condensations and bordering populations of maturing chondrocytes. Thes e studies provide evidence that in early skeletal development, PTPPBS gamma may regulate the rate of chondroblast proliferation in the cartilaginous s keleton.