736 Potential Role for Biglycan in Bone Formation During Fracture Healing

Friday, March 23, 2012: 10:45 a.m. - 12:15 p.m.
Presentation Type: Oral Session
E.L. PINNOW, A.D. BERENDSEN, T.M. KILTS, and M.F. YOUNG, Craniofacial and Skeletal Disease Branch, NIDCR, National Institutes of Health, Bethesda, MD
Objectives: Fracture healing involves a sequence of physiological events, including hematoma formation, inflammation, callus formation, neovascularization, osteoblastic callus mineralization, and osteoclastic remodeling of the bone. This process results in the formation of new lamellar bone in the fracture area. Biglycan (Bgn) is a member of the Small Leucine-Rich Proteoglycan (SLRP) family that is highly enriched in bone. Bgn-deficient mice have decreased bone mass due to lower levels of bone formation. In an effort to further understand the role Bgn has on bone formation, we created fractures and analyzed the process of healing over time. 

Methods: 6-week-old male wild-type (WT) and Bgn-deficient mice were used. Fractures were induced using a standardized fracture device with a 250g weight released from a height of 29cm creating oblique fractures to the right femur. WT and Bgn-deficient mice were analyzed at 7 and 14 days post-fracture by X-ray analysis, histology, and immunohistochemistry. RNA was extracted from the callus at 7 days, and subjected to RT-PCR using primers for Vascular Endothelial Growth Factor (VEGF).

Results: The formation of a fracture callus was observed at both 7 and 14 days post-fracture in both WT and Bgn-deficient mice, showing the largest sizable difference at 14 days. Bgn-deficient mice appeared to have a smaller callus, including less cartilage and woven bone. Immunohistochemistry revealed that Bgn is expressed in the fracture callus of WT mice, localized to the area surrounding woven bone and cartilage. RT-PCR and immunohistochemistry of 7 days post-fracture mice showed a significant decrease of relative VEGF mRNA and protein expression in the callus area of Bgn deficient mice compared to the WT. 

Conclusions: These results suggest that Bgn could play an important role in the process of bone formation during fracture healing, and further, that diminished angiogenesis could be the cellular basis for this impairment.


This abstract is based on research that was funded entirely or partially by an outside source: IRP of the NIDCR, NIH, HHS 1 Z01 DE000379-21

Keywords: Animal, Bone, Bone repair, Extracellular matrix molecules and Regeneration
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