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Are Endogenous BMPs Necessary for Bone Healing during Distraction Osteogenesis?

  • Symposium: Tribute to Dr. Marshall Urist: Musculoskeletal Growth Factors
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Previous reports suggest the application of exogenous BMPs can accelerate bone formation during distraction osteogenesis (DO). However, there are drawbacks associated with the use of exogenous BMPs. A possible alternative to the use of exogenous BMPs is to upregulate the expression of endogenous BMPs. Since DO results in spontaneously generated de novo bone formation in a uniform radiographic, histological, and biomechanical temporal sequence, a genetically engineered model lacking endogenous BMP2 should have measurable deficits in bone formation at different time points. We performed DO on BMP2 fl/+ and BMP2 fl/+ cre mice using a miniature Ilizarov fixator. Distracted samples were collected at various time points and analyzed using Real Time-quantitative PCR, μCT, radiology, immunohistochemistry, histology, and biomechanical testing. Immunohistochemical studies of 34-day heterozygous samples showed reduced expression of BMP2, BMP7, BMPR1a, ACTR1, and ACTR2b. μCT analysis of 51-day heterozygous samples revealed a decrease in trabecular number and increase in trabecular separation. Biomechanical testing of 51-day heterozygous samples revealed decreased stiffness and increased ultimate displacement. Radiological analysis showed the heterozygotes contained a decreased bone fill score at 17, 34, and 51 days. These data suggest endogenous BMPs are important for bone healing and manipulating endogenous BMPs may help accelerate bone consolidation during DO.

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Acknowledgements

We thank members of Dr. St-Arnaud’s lab, Fares Hamade, Tasima Haque, Maria Kotsioprifitis, and Noémi Dahan for assisting with the study, Dr. Vicki Rosen (Harvard School of Medicine, Boston, MA) for the conditional BMP2 knockout mice, Guylaine Bedard and Mark Lepik for help with figures, and the McGill Bone Centre for their assistance with the radiology/μCT and biomechanical testing analysis.

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Authors and Affiliations

  1. Division of Orthopaedics, Shriners Hospital for Children, Montréal, QC, Canada

    Norine Alam MS

  2. Genetics Unit, Shriners Hospital for Children, McGill University, Montréal, QC, Canada

    René St-Arnaud PhD

  3. Division of Orthopaedics, Montréal Children’s Hospital, Montréal, QC, Canada

    Dominique Lauzier AS

  4. Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA

    Vicki Rosen PhD

  5. Division of Orthopaedics, Shriners Hospital and Montreal Children Hospital, McGill University, 1529 Cedar Avenue, Montréal, QC, H3G 1A6, Canada

    Reggie C. Hamdy MD, FRCSC

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  1. Norine Alam MS
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  2. René St-Arnaud PhD
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  3. Dominique Lauzier AS
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  4. Vicki Rosen PhD
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  5. Reggie C. Hamdy MD, FRCSC
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Corresponding author

Correspondence to Reggie C. Hamdy MD, FRCSC.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownerships, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. This work was supported by Shriners of North America operating grant no. 8700.

Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the Shriners Hospital for Children and the Montréal Children’s Hospital of McGill University, Montréal, QC, Canada.

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Alam, N., St-Arnaud, R., Lauzier, D. et al. Are Endogenous BMPs Necessary for Bone Healing during Distraction Osteogenesis?. Clin Orthop Relat Res 467, 3190–3198 (2009). https://doi.org/10.1007/s11999-009-1065-6

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  • DOI: https://doi.org/10.1007/s11999-009-1065-6

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