Evidence that the protein tyrosine phosphatase (PC12,Br7,Sl) gamma (-) isoform modulates chondrogenic patterning and growth.

ABSTRACT

One of the earliest events in bone morphogenesis is the condensation of embryonic mesenchymal cells into chondroblasts and their subsequent proliferation and differentiation into chondrocytes. During this time, certain signaling cascades operate to establish proper patterning and differentiation of the cartilaginous skeleton. Characterization of the signaling pathways involved in these processes remains to be accomplished. We have identified a novel murine cytosolic tyrosine phosphatase termed PTPPBS gamma (+/-) which is a member of the PTP PC12,Br7,Sl (PTPPBS) family. Spatio-temporal expression analysis of the members of this tyrosine phosphatase family demonstrates significant expression of the gamma (-) splice variant in the cartilaginous 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 antisense 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 gamma antisense-treated explants, bromodeoxyuridine-pulse labeling studies revealed increased proliferation of chondroblasts bordering along precartilaginous condensations and bordering populations of maturing chondrocytes. These studies provide evidence that in early skeletal development, PTPPBS gamma may regulate the rate of chondroblast proliferation in the cartilaginous skeleton.