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

Autor: Lahr CA; Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia.; Department of Orthopaedic Surgery, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany., Wagner F; Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia.; Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstrasse 4, 80337, Munich, Germany., Shafiee A; Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia., Rudert M; Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstrasse 4, 80337, Munich, Germany., Hutmacher DW; Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia., Holzapfel BM; Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia. b-holzapfel.klh@uni-wuerzburg.de.; Department of Orthopaedic Surgery, University of Wuerzburg, Koenig-Ludwig-Haus, Brettreichstrasse 11, 97074, Wuerzburg, Germany. b-holzapfel.klh@uni-wuerzburg.de.
Jazyk: angličtina
Zdroj: Calcified tissue international [Calcif Tissue Int] 2019 Sep; Vol. 105 (3), pp. 331-340. Date of Electronic Publication: 2019 Jun 18.
DOI: 10.1007/s00223-019-00574-5
Abstrakt: 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 mm 3 vs. 365 mm 3 , 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.
Databáze: MEDLINE