Abstract |
The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.
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Authors | Janette N Zara, Ronald K Siu, Xinli Zhang, Jia Shen, Richard Ngo, Min Lee, Weiming Li, Michael Chiang, Jonguk Chung, Jinny Kwak, Benjamin M Wu, Kang Ting, Chia Soo |
Journal | Tissue engineering. Part A
(Tissue Eng Part A)
Vol. 17
Issue 9-10
Pg. 1389-99
(May 2011)
ISSN: 1937-335X [Electronic] United States |
PMID | 21247344
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- MMP2 protein, human
- Matrix Metalloproteinase 2
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Topics |
- Adipose Tissue
(metabolism, pathology)
- Animals
- Bone Cysts
(chemically induced, metabolism, pathology)
- Disease Models, Animal
- Femoral Fractures
(metabolism, pathology, therapy)
- Femur
(metabolism, pathology)
- Humans
- Male
- Matrix Metalloproteinase 2
(adverse effects, pharmacology)
- Osteogenesis
(drug effects)
- Rats
- Rats, Inbred Lew
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