Effect of HIP/RPL29 absence on adult bone properties in mice

Sloofman, Laura
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University of Delaware
Ribosomal proteins (RPs) play an important role in the maintenance of a normal protein synthetic rate. Our group generated the first viable mouse mutant model lacking an individual ribosomal protein, HIP/RPL29. Decreased rates of proliferation and protein synthesis in these mutants resulted in skeletal growth defects leading to short stature at birth, which persist during adulthood. We used HIP/RPL29 knockout mice to elucidate the role of this protein in bone structure and rigidity. We hypothesized that a decrease in protein biosynthesis affecting matrix production in HIP/RPL29 knockout mice lowers bone mass and increases bone fragility. Cortical bone microstructure of HIP/RPL29-deficient and wild type six-month-old femurs was assessed at the mid-shaft using micro-computed tomography (micro-CT). Significant differences in the bone composition were found between the HIP/RPL29-null and control mice. Interestingly, we observed a partial preservation of cortical thickness in male samples, coupled with significant increases in bone mineral content. This observation was only found in male samples, indicating a gender-specific effect of HIP/RPL29 deletion on cortical bone parameters. Additionally, null males, and females to a lesser extent, showed increased bone material toughness to compensate for their decreased size. Despite these gender-modulated differences, neither males nor females could withstand comparable forces under three-point bending tests. Moreover, smaller post-yield displacements (and therefore increased bone brittleness) were found in HIP/RPL29-null animals relative to controls.