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

Loading...
Thumbnail Image
File version
Author(s)
Lahr, CA
Wagner, F
Shafiee, A
Rudert, M
Hutmacher, DW
Holzapfel, BM
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2019
Size
File type(s)
Location
License
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.

Journal Title
Calcified Tissue International
Conference Title
Book Title
Edition
Volume
Issue
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject
Biochemistry and cell biology
Biomedical engineering
Clinical sciences
Bone grafts
Bone marrow
Bone morphogenetic protein
Osteoinduction
Xenograft model
Persistent link to this record
Citation
Lahr, CA; Wagner, F; Shafiee, A; Rudert, M; Hutmacher, DW; Holzapfel, BM, Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity, Calcified Tissue International, 2019, 105 (3), pp. 331-340
Collections