Analysis on the gene expression of CTGF, an endochondral ossification factor, during mouse development and its application for a bone regeneration

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CTGF/Hcs24 is a cystein-rich novel multifunctional growth factor which belongs to CCN gene family. We prepared Dig-, 35S-labeled riboprobes to analyze CTGF gene expression pattern during mouse development by in situ hybridization. CTGF gene was expressed as 2 waves in development, the first peek of the wave was exhibited around E9 in somites and the second wave ascended from E13 mainly depended on a start of the endochondral ossification. A site specific CTGF gene expression was observed in the hypertrophic chondrocytes through the endochondral ossification, whereas expression in the endothelial cells of blood vessels was observed in every stages. In the case of Cbfal deficient mice, which resulted a skeletal abnormality in the calcification, CTGF was never expressed in the anlage of endochondral bones. We concluded that CTGF has dual possible roles in development, one is an unknown role in early development, another role is as an essential factor of hypertrophic chondrocytes differentiation during endochondral ossification.In the next study, we established transgenic(Tg) mice that over produce CTGF under the control of mouse type XI collagen promoter. Tg mice could develop and grow normally. But they showed dwarfism within a few months after birth. X-ray analysis revealed that their bone density was decreased compared with normal mice. The femurs in the hind limbs in particular showed an apparent low density. These results indicated that over expression of CTGF affects certain steps of endochondral ossification. In addition, the testes were much smaller than normal and fertility was affected in Tg mice, indicating that CTGF/Hcs24 may also regulate the embryonic development of the testes.