Mechanobiological Regulation of Cortical Bone in Vertebrates

Purdue University, West Lafayette IN

Investigators

Abstract

Diversity in skeletal form amongst vertebrate animals results from a combination of genetic and environmental influences during growth and aging. Mechanical stimuli, caused by physical activity, represent a potent environmental influence that regulates bone growth and remodeling. "Warm-blooded" mammals and birds may be able to maintain relatively light skeletons compared to "cold-blooded" reptiles and amphibians because their bone cells are inherently more responsive to mechanical loading. However, it is unclear if the differences in skeletal response are caused by differences in the bone cells, differences in the metabolic rate of "cold" and "warm" blooded animals, or a combination of both. The award will investigate the relative adaptive potential of the skeleton among different terrestrial vertebrates and determine the underlying physiological, anatomical, and genetic regulatory factors influencing adaptive bone formation. This work will be critical for understanding evolutionary diversity in skeletal form among mammals and birds and the relative conservation of skeletal structure in modern "cold-blooded" vertebrates compared to ancient (fossil) examples. Novel molecules regulating bone formation, which could have important biomedical applications for treating bone loss, will be measured. The results of this work will be presented to the public through lectures, university websites, and through learning modules to teach local elementary and junior high school students science and engineering concepts. The objective of this research is to relate regulation of the mechanosensitive Sost-Wnt/beta-catenin pathway, specific to osteocyte-induced skeletal anabolism, to the bone tissue response to physical stimuli in the skeletons of four species from three terrestrial vertebrate groups (reptiles, birds, mammals) under artificial tibial loading. The multi-scale gene- to tissue-level approach used here will utilize in vivo bone functional adaptation models, in vitro bone tissue organ culture models, 3D confocal microscopy, and transcriptomic analyses to establish a comparative understanding of molecular and cellular mechanobiological mechanisms in the vertebrate skeleton, the influence of animal metabolism on organismal response to environmental challenges, and factors influencing structural diversity across different vertebrate groups.