The effect of MS-818, newly synthesized pyrimidine compound, on fracture repair.

Both periosteal cell proliferation and endochondral ossification accompanied are characteristic of the fracture healing process. This process is regulated by various kinds of soluble factors including prostanoids, cytokines and growth factors. In particularly, basic fibroblast growth factor (bFGF) stimulates the mesenchymal cell proliferation and differentiation in the periosteum and leads to the fracture healing. Recently, newly synthesized pyrimidine compound, 2-piperadino-6-methyl-5-oxo-5,6-dihydro (7H) pyrrolo [3,4-d] pyrimidine maleate (MS-818) has been reported to augment the biological effect of bFGF in vitro. Therefore, we have studied the effect of MS-818 on fracture healing process in which bFGF has been reported to play an important role. In the rat fracture model, 5 mg/kg MS-818 which had been administered intraperitoneally for fourteen consecutive days enhanced the cartilage matrix formation. In the bone defect model, in which we can find only membranous ossification without chondrogenesis, cartilage matrix formation was observed in seven days after 1 microgram of human bFGF containing polymer pellet was embedded in the defect site. Chondrogenesis induced by bFGF was enhanced significantly after 5 micrograms MS-818 containing pellet was implanted with bFGF pellet. These results suggest that MS-818 might promote the fracture healing process through enhancement of the effect of bFGF on endochondral ossification.