Masahiro Kumagai

ENHANCEMENT OF ECTOPIC BONE FORMATION IN MICE WITH A DEFICIT IN FAS-MEDIATED APOPTOSIS

Bone tormation is under the control of cytokines as well as growth factors such as bone morphogenetlc protelns (BMP). This suggests the possibillity that osteogenesls might be modulated by factors which atso modulate the Immune system. To test whether Immune disorders In the host may influence bone formation, we studied BMP‐Induced bone formation In a C3H/HeJ strain of mice benring a mutant gene, the lymphoproliteration Qene (lpr) or the genemlbed lym‐phoprolifarative diseaee gene (gld), both of which are known to be a Fas delaion mutant and a Fas ligand mutant, respectively, and to Induce Immune disorders vla a deficit In Fas‐mediated apoptoak Crude BMP derived from bovine bone were injscted into the muscular tlasue In the femur of adult C3H/HaJ mice or C3H/HeJ mice bearing an lpr or gld gene. Quantltathre analysis of the resulting ectopic bone formation by X‐ray photography 2 weeks after infection revealed that the presence of either the Ipr or gld gene caused a bone mess dgnlficantly larger In dimension than that seen in the wiid type mice. Histologlcal examlnatlon also revealed the dmerent Influence between these mutant genes on the level of bone fofmatlon exhibited by hyallne cartilage and bone imbeculae. Based on these results, we discussed the possible mechanisms of the enhanced ectopic bone fotmation under the deficit In Fas‐medlated apoptosls.