Characterization of fracture healing in myocardin-related transcription factor-A deficient mice
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INTRODUCTION: A recent area of interest has become adipose tissue of the bone marrow. Unlike fat found elsewhere in the body, it is able to respond to its microenvironment by expanding, contracting, and even releasing hormones of its own. The marrow adipose tissue (MAT) increases with age and even within anorexic patients. Changes in MAT may be directly linked to bone tissue, since both adipocytes and osteoblasts share a common progenitor cell population. This is supported by recent results showing that the constitutive deletion of the MRTF-A (Myocardin related transcription factor A) gene not only led to leaner mice leaner but also had a bone phenotype. The bones were shorter and had decreased bone mass; the female mice were more susceptible to osteopenia. It is unclear as to how this bone phenotype will respond to fracture repair, a coordinated process that is dependent upon differentiation toward the osteoblast lineage. Therefore, both male and female MRTF-A knockout (KO) and wild type (WT) mice were examined in a fracture study. METHODS: Male and female mice (KO and WT) aged 8-16 weeks were fractured using a closed, stabilized fracture model. Tissues were harvested as post-operative day 14, 21, and 37. Radiographic films and histological assessment were completed at each time point to visualize the progression of fracture repair. Gene expression studies using RT-qPCR were all done at time points 14 and 37. Results were compared between genotype and sex. RESULTS: Fracture calluses between WT and KO male and female mice appeared nearly identical via X-ray, suggesting that MRTF-A did not affect fracture repair. Only at the later time points did the histology show females had increased MAT regardless of genotype. Immunofluorescence with perilipin further confirmed this. Adipogenic, chondrogenic, and osteogenic markers also yielded differences in relative mRNA expression between the sexes. CONCLUSIONS: The MRTF-A KO mice did not show delayed or altered fracture repair compared to the WT mice. However, the data suggest difference in MAT deposition between male and female mice. Further work is necessary to fully understand this sex difference.