Bone morphogenetic protein-7 enhances bone-tendon integration in a murine in vitro co-culture model

Abstract

Purpose: Bone-tendon healing following anterior cruciate ligament reconstruction is reportedly enhanced by bone morphogenetic protein (BMP)-7. To improve our understanding of the underlying biologic processes, we examined the effects of BMP-7 on region-specific gene expression in vitro.

Methods: A murine in vitro co-culture model simulating the osteoblast, interface and fibroblast regions was established. The dose- and time-dependent region-specific effects of BMP-7 exposure on gene expression of Alpl, Bglap, Col1a1, Runx2 and Spp1 were analysed by quantitative PCR.

Results: At the osteoblast region, BMP-7 significantly increased Alp, Bglap, Col1a1, and Runx2 expression, while Spp1 expression was suppressed. At the interface region, BMP-7 exposure resulted in a trend towards increased expression rates of Alpl and Col1a1, whereas Bglap (P < 0.001) and Runx2 (P < 0.01) were significantly upregulated without any detectable effect on Spp1 expression. At the fibroblast region, BMP-7 increased Alpl (P < 0.001), Bglap (P < 0.001) and Runx2 (P < 0.001) expression, but no significant effects were seen on Col1a1 or Spp1. Exposure to BMP-7 (100 ng/ml) had its most pronounced biologic impact on day ten.

Conclusion: BMP-7 stimulation showed beneficial region-specific effects on bone-tendon healing in vitro, such as enhanced expression of parameters for ossification and fibroblast transdifferentiation, both key processes during successful graft integration.