ABSTRACT
BACKGROUND@#The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. @*METHODS@#Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. @*RESULTS@#Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. @*CONCLUSION@#We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.
ABSTRACT
BACKGROUND@#The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. @*METHODS@#Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. @*RESULTS@#Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. @*CONCLUSION@#We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.
ABSTRACT
OBJECTIVES: Orphan nuclear receptor small heterodimer partner (SHP) is involved in osteoblastic differentiation. This study was undertaken to demonstrate a role of SHP in in vivo bone development using microcomputed tomographic (microCT) analysis of SHP knockout (KO) mice. MATERIAL & METHODS: Tibia bones were harvested from 1-, 4-, 8- and 20-week-old wild type (WT) and SHP KO mice. The microarchitecture of tibial bone was analyzed using a microCT (Skyscan 1172; Skyscan, Kontich, Belgium). Samples were scanned at a resolution of 17 microm (isotropic). The X-ray was operated with 50 kV, 200 microA of energy, 1.2 sec of exposure time, and a 0.5 mm thick aluminum filter. Projections were acquired over an angular range of 180degrees. For quantification of the bone mineral density (BMD), the microCT was calibrated using 2 standard phantoms with densities of 0.25 and 0.75 g/cm3. The image slices were reconstructed and analyzed using CT analyzer software (CTan, Skyscan). RESULTS: The CT values of tibial trabecular bone were significantly decreased in SHP KO compared to WT at 20-week-old mice determined by microCT; (bone volume / tissue volume [BV/TV, 40%], BMD [80%], and trabecular number [Tb.N, 50%]). However, the CT values were not significantly different between WT and SHP KO in cortical bone. Furthermore, the qualitative indices of trabecular bone such as the structure model index (SMI) and the polar moment inertia (PMI) did not differ between WT and SHP KO mice. CONCLUSION: These microCT results supports that SHP may act as a positive regulator of trabecular bone formation.