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Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity

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Abstract

This study aimed to investigate the effects of recombinant human bone morphogenetic protein (rhBMP-7) on human cancellous bone grafts (BGs) while differentiating between anabolic and catabolic events. Human BGs alone or supplemented with rhBMP-7 were harvested 14 weeks after subcutaneous implantation into NOD/Scid mice, and studied via micro-CT, histomorphometry, immunohistochemistry and flow cytometry. Immunohistochemical staining for human-specific proteins made it possible to differentiate between grafted human bone and newly formed murine bone. Only BGs implanted with rhBMP-7 formed an ossicle containing a functional hematopoietic compartment. The total ossicle volume in the BMP+ group was higher than in the BMP− group (835 mm3 vs. 365 mm3, respectively, p < 0.001). The BMP+ group showed larger BM spaces (0.47 mm vs. 0.28 mm, p = 0.002) and lower bone volume-to-total volume ratio (31% vs. 47%, p = 0.002). Immunohistochemical staining for human-specific proteins confirmed a higher ratio of newly formed bone area (murine) to total area (0.12 vs. 0.001, p < 0.001) in the BMP+ group, while the ratio of grafted bone (human) area to total area was smaller (0.14 vs. 0.34, p = 0.004). The results demonstrate that rhBMP-7 induces BG resorption at a higher rate than new bone formation while creating a haematopoietic niche. Clinicians therefore need to consider the net catabolic effect when rhBMP-7 is used with BGs. Overall, this model indicates its promising application to further decipher BMPs action on BGs and its potential in complex bone tissue regeneration.

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Acknowledgements

Baxter Healthcare Australia kindly provided Fibrin Glue (TISSEEL Fibrin Sealant). The following funding existed during conduction of this study: National Health and Medical Research Council of Australia (Project Grant 1082313 to BMH and DWH), German Research Foundation (DFG HO 5068/1-1 to BMH) and Australian Research Council (IC160100026).

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Authors and Affiliations

  1. Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia

    Christoph A. Lahr, Ferdinand Wagner, Abbas Shafiee, Dietmar W. Hutmacher & Boris Michael Holzapfel

  2. Department of Orthopaedic Surgery, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany

    Christoph A. Lahr & Boris Michael Holzapfel

  3. Department of Pediatric Surgery, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University Munich, Lindwurmstrasse 4, 80337, Munich, Germany

    Ferdinand Wagner & Maximilian Rudert

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  1. Christoph A. Lahr
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Correspondence to Boris Michael Holzapfel.

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Christoph A. Lahr, Ferdinand Wagner, Abbas Shafiee, Maximilian Rudert, Dietmar W. Hutmacher and Boris Michael Holzapfel declare that there is no conflict of interest.

Human and Animal Rights and Informed Consent

This study was approved by the University Animal Ethics Committee (Approval No. 130/025). All animal experiments were executed in conformity with the national animal care guidelines.

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Lahr, C.A., Wagner, F., Shafiee, A. et al. Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity. Calcif Tissue Int 105, 331–340 (2019). https://doi.org/10.1007/s00223-019-00574-5

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