The role of hcs-24, a newly isolated hypertrophic chondrocyte-specific gene, in endochondral ossification

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1) cDNA of hypertrophic chondrocyte specific gene hcs-24 was isolated. The nucleotide sequence of coding region of hcs-24 was completely the same as that of connective tissue growth factor (CTGF).2) Expression of hcs-24/ctgf in rabbit growth cartilage cells in culture was highest in hypertrophic stage. The gene expression in chondrocytic cells was stimulated by TGFbeta and BMP-2.3) Immunohistochemical techniques revealed that hypertrophic chondrocytes and endothelial cells in cost-chondral junctions of mouse ribs were stained with anti-CTGF antibody in vivo. Surface of and chondrocyte clusters in articular cartilge of arthritis were also stained with the antibody.4) During development of mouse embryos, mRNA level of hcs-24/ctgf reached a maximum at E7, decreased gradually and then increased again at E17.HCS-2/8 cells transfected with an hcs-24 expression vector grew rapidly than non-transfected cells. The abilities to proliferate and migrate of vascular endothelial cells transfected wi … More th expression vectors that generate anti-sense RNA of CTGF cDNA were markedly lower than those of control.6) Purified CTGF and recombinant CTGF stimulated the proliferation and proteoglycan synthesis of chondrocytes and alkaline phosphatase in chondrocytes and osteoblasts. The growth factor simulated the proliferation and migration of vascular endothelial cells. These effects were inhibited by anti-CTGF antibody.7) An ELISA system to measure Hcs-24/CTGF was established.8) Two types of specific binding sites of ^<125>I-rCTGF were identified on HCS-2/8 cells. The binding of ^<125>I-rCTGF to rabbit growth cartilage cells in culture was maximal in growth phase and decreased as they differentiated.9) Transgenic mice of OCNT/CTGF had skeletal disorder.These findings suggest that Hcs-24/CTGF synthesized by hpertrophic chondrocytes stimulates the proliferation and maturation of proliferative chondrocytes and hypertrophy of mature chondrocytes and induces angiogenesis into cartilage from bone, resulting in promotion of endochondral ossification. The factor may also be involved in organogenesis in embryos. Less