Analysis of the function of PTHrP in tooth development.

点击翻译按钮获取中文摘要

Gene expression of PTHrP was observed in the enamel organ of rat tooth germ, whereas that of its receptor, PTH/PTHrP receptor, was in the dental papilla and surrounding mesenchyme. When the mouse tooth explants were cultured with antisense oligodeoxynucleotide (ODN) against mouse PTHrP mRNA in serum-free medium, the invasion of bone tissue was observed in the tooth germs as follows. At 5-6 days in culture, the bone tissue extending from outside of tooth germ began to invade into the dental papilla. The invasion of bone tissue into developed extensively during the culture period and the invasion occurred also into enamel organ. During 10-21 days in culture the tooth germs were destroyed by the extensive invasion of bone tissue. On the other hand, the explants cultured without ODN,with sense ODN or with antisense ODN plus recombinant human PTHrP showed normal histological structure as observed in vivo. Antisense ODN for mouse PTH/PTHrP receptor also induced the bone invasion into the tooth germs as observed in the explants treated with antisense ODN for PTHrP.The treatment with antisense ODN for PTHrP induced the reduction of TRAP (tartrate-resistant acid phophatase) activity in osteoclasts in the explants and suppressed the formation of dental sac, sugesting that the reductions in osteoclast activity and in dental sac formation are involved in the bone invasion induced the antisense-treatment.Results suggest that PTHrP is essential for the tooth development and for the protection of tooth germs from the invasion of bone tissues.