Abstract
Introduction and Aims: There is cumulative evidence that BMP-14 has a role in chondrocyte maturation in endochondral ossification of growth plate. We hypothesise that BMP-14 has a similar role in bone regeneration following fracture. We aim to compare normal versus a gene knock-out mouse to demonstrate histologic, radiographic and biochemical deficiencies in the mouse that lacks the gene for BMP-14.
Method: The brachypodism (bp) mouse has a homozygous form (BMP-14 −/−) that does not express BMP-14 and a heterozygous form (BMP-14 +/−) that does. Closed midshaft femur fractures were created and stabilised in eight-week female mice in both types of mice. Mice were euthanised at differing time points and the femurs harvested for DNA, proteoglycan, collagen determinations. Histology was performed with Tri-Chrome staining. Radiographs were taken at each time point to evaluate callus formation. Analysis for all quantitative measures was normalised and statistically evaluated using a two-way ANOVA.
Results: Biochemical results show BMP-14 deficient (bp) mice having a five to seven-day delay in attaining peak values of DNA compared with controls. The time-dependent change of cellular proliferation reached significance. Peak values of proteoglycan content were three times less in the bp mouse in the early phase of healing in the bp mouse. Histologically, the BMP-14-deficient animals exhibited a delay in peak area of callus and callus organisation in the regenerating femur fracture. Radiographic analysis shows peak callus area was delayed two weeks, and had a decreased magnitude over that two-week span in the bp mice. Callus was less evident in the bp for time points throughout the study.
Conclusion: We have produced evidence in this animal model that deficiency of BMP-14 is associated with a short-term delay in fracture healing. We also can demonstrate that there is a delay in cellular recruitment and chondrocyte differentiation in the first two weeks of fracture repair in the bp mouse. These results support our hypothesis that BP-14 has a significant role in fracture repair. There may be a use for BMP-14 in assisting long-bone fracture repair.
These abstracts were prepared by Editorial Secretary, George Sikorski. Correspondence should be addressed to Australian Orthopaedic Association, Ground Floor, The William Bland Centre, 229 Macquarie Street, Sydney, NSW 2000, Australia.
At least one of the authors is receiving or has received material benefits or support from a commercial source.
