Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice.

Daniel S Oristian, Laura G Sloofman, Xiaozhou Zhou, Liyun Wang, Mary C Farach-Carson, Catherine B Kirn-Safran

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2009 Jan

filter terms:

Mice lacking HIP/RPL29, a ribosomal modulator of protein synthesis rate, display a short stature phenotype. To understand the contribution of HIP/RPL29 to bone formation and adult whole bone mechanical properties, we examined both developing and adult bone in our knockout mice. Results indicated that bone shortening in HIP/RPL29-null mice is due to delayed entry of chondro-osteoprogenitors into the cell cycle. Structural properties of adult null bones were analyzed by micro-computed tomography. Interestingly, partial preservation of cortical thickness was observed in null males indicating a gender-specific effect of the genotype on cortical bone parameters. Null males, and to a lower extent null females, displayed increased bone material toughness to counteract decreased bone size. This elevation in a bone material property was associated with increased bone mineral density only in null males. Neither male nor female null animals could withstand the same maximum load as gender-matched controls in three-point bending tests, and smaller post-yield displacements (and thus increased bone brittleness) were found for null animals. These results suggest that HIP/RPL29-deficient mice exhibit increased bone fragility due to altered matrix protein synthesis rates as a consequence of ribosomal insufficiency. Thus, sub-efficient protein translation increased fracture risk in HIP/RPL29-null animals. Taken together, these studies provide strong genetic evidence that the ability to regulate and amplify protein synthesis rates, including those proteins that regulate the cell cycle entry during skeletal development, are important determinants for establishment of normal bone mass and quality.

Citation

Daniel S Oristian, Laura G Sloofman, Xiaozhou Zhou, Liyun Wang, Mary C Farach-Carson, Catherine B Kirn-Safran. Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2009 Jan;27(1):28-35