Bone morphogenetic protein 2 accelerates osteointegration and remodelling of solvent-dehydrated bone substitutes.

INTRODUCTION: lt was the purpose of this study to investigate how bone morphogenetic protein 2 (BMP-2) influences remodelling and the biomechanics of solvent-dehydrated bone in the long run. Furthermore, the early influence of this growth factor on the substitute was investigated. MATERIALS AND METHODS: Using a weight-bearing animal model, solvent-dehydrated bone was implanted in the tibial head of merino sheep ( n=12) after being loaded with BMP-2 (100 microg/100 microl). At 4 weeks ( n=6) and 9 months ( n=6) after surgery, histomorphological, histomorphometrical and biomechanical investigations were performed. RESULTS: At 9 months after implantation of BMP-2-loaded specimens, the bone per tissue volume was high, with levels above those of physiological cancellous bone. The amount of remaining solvent-dehydrated bone was markedly decreased, and in contrast, the amount of newly formed bone was extremely high. The specimen degradation had already occurred within the first 4 weeks after implantation, showing no further impact throughout the 9-month period. Biomechanical investigations at 9 months after implantation demonstrated a yield strength which achieved levels at least equivalent to physiological cancellous bone. BMP-2 showed no significant impact on the biomechanical properties after 4 weeks, compared to specimens prior to implantation. CONCLUSION: BMP-2 predominantly has an impact on the early implant degradation as well as bone formation, which leads to an almost completed bone remodelling of the solvent-dehydrated specimen within the study period of 9 months.

Osteogenic protein-1 (OP-1) blocks cartilage damage caused by fibronectin fragments and promotes repair by enhancing proteoglycan synthesis.

OBJECTIVE AND DESIGN: The abilities of osteogenic protein-1 (OP-1) and TGF-beta1 to affect cartilage damage caused by fibronectin fragments (Fn-fs) that are known to greatly enhance cartilage proteoglycan (PG) degradation were compared. MATERIAL: Articular cartilage was obtained from 18 month old bovines. TREATMENT: To test blocking of damage, cartilage was cultured with or without OP-1 or TGF-beta in the presence of 100 nM Fn-fs. To test restoration of PG, cartilage was first cultured with Fn-fs and the cartilage then treated with factors. METHODS: Cartilage PG content was measured in papain digests using the dimethylmethylene blue assay. PG synthesis was measured by incorporation of 35S labeled sulfate. RESULTS: OP-1 blocked damage and restored PG in damaged cartilage, apparently due to enhanced PG synthesis. However, TGF-beta1 alone decreased PG content. CONCLUSIONS: These results clearly demonstrate differences between OP-1 and TGF-beta1, both members of the TGF-beta superfamily and illustrate the efficacy of OP- in blocking Fn-f mediated damage.

Effects of recombinant human osteogenic protein 1 on the production of proteoglycan, prostaglandin E2, and interleukin-1 receptor antagonist by human articular chondrocytes cultured in the presence of interleukin-1beta.

OBJECTIVE: Recombinant human osteogenic protein 1 (OP-1) is an effective stimulator of human cartilage 35S-proteoglycan synthesis. The present study was conducted to determine whether stimulation of human articular chondrocytes with OP-1 can help overcome interleukin-1beta (IL-1beta)-induced suppression of 35S-proteoglycan synthesis. METHODS: Human articular chondrocytes in alginate beads were maintained for 3 days in the absence (control) or presence of IL-1beta at 0.1-100 pg/ml with or without OP-1 at 50 ng/ml, in medium containing 10% fetal bovine serum (FBS). Incorporation of 35S-sulfate into proteoglycans was quantified during the last 4 hours of culture and reported as counts per minute per microg DNA. Release of interleukin-1 receptor antagonist (IL-1Ra) and prostaglandin E2 into the medium was monitored by immunoassay. RESULTS: IL-1beta at 10 pg/ml caused a 60% decrease in 35S-proteoglycan synthesis. This could be blocked by including 500 ng/ml IL-1Ra in the medium. The presence of 50 ng/ml OP-1 in the IL-1beta-containing medium was effective in restoring 35S-proteoglycan synthesis to the level of that found in cultures not treated with IL-1beta. The restorative effects of OP-1 and IL-1Ra were cumulative. The rate of release of prostaglandin E2 and IL-1Ra into the medium was not affected by the presence of OP-1. CONCLUSION: Treatment of human articular chondrocytes with OP-1 cultured in the presence of FBS is effective in overcoming the down-regulation of proteoglycan synthesis induced by low doses of IL-1beta.