Analysis of gene expression pattern and extracellular environment of connective tissue growth factor (CCN2/CTGF) during secondary ossification center formation

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CCN2/connective tissue growth factor (CCN2) is a critical signaling modulator of mesenchymal tissue development. This study investigated the localization and expression of CCN2 as a factor supporting angiogenesis and chondrogenesis during development of secondary ossification centers in the mouse tibial epiphysis. Immunostaining showed that CCN2 was distributed broadly around the expressed cells located in the central region of the epiphysis, where the chondrocytes become hypertrophic and the cartilage canal enters into the hypertrophic mass. Furthermore, an overlapping distribution of metalloproteinase (MMP)9 and Heparan sulfate proteoglycan(Perlecan) and CCN2 was found in the secondary ossification center. These findings suggest that the CCN2 is involved in establishing epiphyseal vascularization and remodeling, which eventually determines the secondary ossification center in the developing epiphysial cartilage