CAREER: Osteocyte Regulation of Bone Tissue Fracture Resistance

Montana State University, Bozeman MT

Investigators

Abstract

This Faculty Early Career Development (CAREER) project will support research that intends to improve our understanding of how osteocytes - strain-sensing cells embedded in bone tissue - regulate bone material properties and fracture resistance. Therapies for managing bone fragility target the maintenance of bone mass. However, bone fragility is not fully explained by bone loss but also depends on the quality of bone matrix. Osteocytes play several important roles in regulating bone matrix properties, but several urgent questions must be addressed before interventions can be designed that act on these cells to improve the bone matrix quality and the resulting tissue fracture resistance. This project will determine how osteocytes toughen bone tissue through acting on other bone cells as well as by their direct interactions with the surrounding bone matrix. Knowledge gained during this project will lay the foundation for developing a new class of therapies that target the improvement of bone matrix quality by osteocytes. The broader impacts of the work are amplified by the creation of a cohort-based program to engage nontraditional Montana State University students in engineering research; and train underrepresented, undergraduate and graduate students. Research data will be integrated into a new advanced biomechanics course as well as into core engineering courses. The overarching goal of this CAREER research project is to advance fundamental knowledge about the regulation of bone matrix by osteocytes. The osteocytes may influence bone matrix material properties and the resulting bone strength and fracture toughness in multiple ways. Osteocytes are well-known to indirectly determine bone matrix properties through their control of osteoclasts and osteoblasts. Osteocytes may also directly determine bone matrix properties by removing and replacing their neighboring bone matrix. The first objective of this project is to determine the impacts of direct and indirect osteocyte regulatory activities on bone matrix composition, material properties, and fracture toughness. These matrix-regulatory activities are stimulated by lactation, loading, and ovariectomy models. The second objective is to define the metabolic processes that underpin different matrix regulatory activities by osteocytes. A combination of targeted and untargeted metabolomic analyses will reveal how osteocytes utilize energy during activities that directly or indirectly impact bone matrix. The knowledge gained from these CAREER studies will lay the foundation for new therapeutic strategies that target the improvement of bone matrix quality through modulating the activities and metabolic processes of the osteocyte. This project is jointly funded by Biomechanics and Mechanobiology and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.