Are endogenous BMPs necessary for bone healing during distraction osteogenesis?
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, lCT, radiology, immunohistochemistry, histology, and biomechanical testing. Immunohistochemical studies of 34-day heterozygous samples showed reduced expression of BMP2, BMP7, BMPR1a, ACTR1, and ACTR2b. lCT 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.
Alam
Norine
N
Division of Orthopaedics, Shriners Hospital for Children, Montréal, QC, Canada.
St-Arnaud
René
R
Lauzier
Dominique
D
Rosen
Vicki
V
Hamdy
Reggie C
RC
D030201:Activin Receptors, Type I / Q000378:metabolism; D030301:Activin Receptors, Type II / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D001861:Bone Regeneration; D018889:Ilizarov Technique / Q000295:instrumentation; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D019857:Osteogenesis, Distraction / Q000295:instrumentation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D013997:Time Factors; D055114:X-Ray Microtomography
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D012333:RNA, Messenger; C525820:bmp7 protein, mouse; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498943:Acvr1 protein, mouse; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; C425584:activin receptor type II-B