BMP-Induced Ectopic Bone Formation in Osteopetrotic(op/op)Mice

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Osteopetrotic(op/op)mice suffer from a severe deficiency of monocytes/macrophages and osteoclants due to a genetic derangement in M-CSF production. In this study, we examined the process of ectopic bone formation by implantation of recombinamnt human BMP-2(rh BMP-2)/insoluble rat bone collagen complex into mice in a macrophage/osteoclast-deficient condition. The rhBMP was produced by use of a baculovirus-insect cell(Sf-9)system. In both op/op mice and their phenotypically normal littermates, not only endochondral but also intramembranous bone was induced 1 week after implanation. At 2 weeks after implantation, the ectopic bone in normal littermates mostly consisted of mature bone with a sign of remodeling. In contrast, the ectopic bone in op/op mice appeared to exhibit the morphological characteristics of woven bone and calcified cartilage as was observed at 1 week, and retained this configuration unchanged at 11 weeks; whereas the ectopic bone in normal littermates was largely resorbed by 11 weeks. We thus conclude that the deficiency of monocytes/macrophages and osteoclasts does not affect the induction of bone/cartilage but results in the failure of the maturation of ectopic bone.
硬組織再生生物学会の論文