Overexpression of connective tissue growth factor hypertrophic chondrocyte-specific gene product 24 decreases bone density in adult mice and induces dwarfism

Connective tissue growth factor/hypertrophic chondrocyte-specific gene prod uct 24 (CTGF/Hcs24) is a multifunctional growth factor for fibroblasts, cho ndrocytes, and vascular endothelial cells. In the present study, we establi shed transgenic (Tg) mice that overproduce CTGF/Hcs24 under the control of mouse type XI collagen promoter. Tg mice could develop and their embryonic and neonatal growth occurred normally. But they showed dwarfism within a fe w months of birth. X-ray analysis revealed that their bone density was decr eased compared with normal mice. The femurs in the hindlimbs in particular showed an apparent low density. These results indicated that overexpression of CTGF/Hcs24 affects certain steps of endochondral ossification. In addit ion, the testes were much smaller than normal and fertility was affected in Tg mice, indicating that CTGF/Hcs24 may also regulate the embryonic develo pment of the testis. (C) 2001 Academic Press.