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

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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.

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Acknowledgments

The study was funded by University Hospitals Giessen and Marburg, according to §2 passage 3 (research funding) of the interhospital cooperation contract.

The authors thank Dr. René Zimmermann and Dr. Nahed El-Najjar for their contributions to the conception of the study, Mrs. Pia Janssen for her invaluable technical assistance and Mrs. Claudia Krappen (Freistil-Design, Geldern, Germany) for graphic design.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Trauma, Hand and Reconstructive Surgery, University of Giessen and Marburg, 35043, Marburg, Germany

    Tim Schwarting, Michael Benölken, Steffen Ruchholtz, Michael Frink & Philipp Lechler

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  1. Tim Schwarting
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  2. Michael Benölken
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  3. Steffen Ruchholtz
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  4. Michael Frink
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Correspondence to Tim Schwarting.

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Schwarting, T., Benölken, M., Ruchholtz, S. et al. Bone morphogenetic protein-7 enhances bone-tendon integration in a murine in vitro co-culture model. International Orthopaedics (SICOT) 39, 799–805 (2015). https://doi.org/10.1007/s00264-015-2688-8

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  • DOI: https://doi.org/10.1007/s00264-015-2688-8

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