Changes of Osteopontin Distribution and Matrix Mineralization during Remodeling in Experimental Bone Formation.

Abstract

When bone is rapidly induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), more noncollagenous proteins (NCPs) are accommodated among the collagen meshwork. These NCPs are then removed, resulting in highly mineralized mature bone. However, few reports have focused on changes in the bone matrix of rhBMP-2-induced bone. In the present study, rhBMP-2 with an artificial carrier was implanted over bone defects in rat calvariae, and changes in the distribution of osteopontin (OPN), the degree of mineralization and speed of bone formation were investigated histochemically and radiographically. Dome-shaped areas of newly formed bone observed at postoperative week 2 were intensely immunoreactive for OPN and intensely labeled with calcein, but were not as radiopaque as the preexisting bone. At postoperative week 8, intense immunoreactivity was detected only on cement lines and in small discrete areas on the flattened domes. The matrix was as radiopaque as, and indistinguishable from, the preexisting bone. Only thin linear labeling of calcein was found on the bone surface. These findings suggest that, in rhBMP-2 induced bone, production of OPN is increased when the rate of bone formation is high, and that OPN produced in the early stage of bone formation is removed during bone remodeling to create a highly mineralized mature bone matrix.