Enhanced Osteoinduction by Intramuscular Grafting of BMP-β-TCP Compound Pellets into Murine Models

抄録

The osteoinductive effects of bone morphogenetic protein (BMP, derived from murine osteosarcoma) were studied with regard to its use combined with β-tricalcium phosphate (β-TCP). BMP and β-TCP were molded into pellets by the “pressure method”, originated by us and transplanted to ddY mice. Control mice received interdorsal muscular implantations of either the BMP or β-TCP pellets. The animals were sacrificed 1, 2 and 3 weeks after grafting, for radiological, histochemical, and ultrastructural observations. The BMP-β-TCP compound pellets induced faster cartilage and bone formation, whereas these activities were slower when pellets made solely of BMP were used. The β-TCP pellets demonstrated no osteoinductive properties. Observations revealed two types of β-TCP resorbing multinuclear giant cells. One was osteoclastic, expressing calcitonin receptors, having numerous mitochondria and ruffled border-like structures; the other was not osteoclastic in nature. In animals grafted with the compound pellets, a great number of osteoclastic cells gathered on the pellets, much earlier than those grafted with the pellets made of BMP alone. Then, osteoblastic bone formation over the cement lines followed an osteoclastic resorption of both β-TCP and newly formed bone. In contrast, BMP induced few osteoclastic cells, resulting in slower bone coupling. Furthermore, the faster bone formation induced by the compound pellets seemed to be associated with the presence of β-TCP. Porous by nature, β-TCP would entrap BMP within its micropores, and thus, the intrinsically diffusible BMP is retained and its action consequently prolonged. In addition, the compound pellet offered increased surface contact between BMP and mesenchymal cells. Therefore, BMP-β-TCP compound pellets induce cartilage and bone formation more rapidly than does BMP alone.