Role of Perlecan in Bone Mechanotransduction Using a Novel Mouse Model

Osteocytes are the most numerous cells in the bone and the most mechanosensitive. Mechanotransduction is the ability of a cell to sense a stimulus and be able to convert that stimuli from mechanical to biochemical signals. α2δ1, a cell surface subunit of voltage sensitive calcium channels (VSCCs) and Perlecan, a large heparan sulfate proteoglycan (HSPG2) interact with osteocytes and are essential for the bone mechanical responses. Our lab has shown that HSPG2 and α2δ1 may form a complex that enables a direct connection between the mineralized matrix of bone and the cell membrane of osteocytes. We want to determine the consequences of Perlecan deletion specifically in osteocytes using a novel Perlecan floxed model (Hspg2f/f). To validate the model, two rounds of breeding were done between Hspg2f/f and mice with Cre under the control of DMP1 to delete Perlecan specifically within osteocytes. Tail snips were taken from mice and DNA isolation and PCR was performed in all samples. To detect loxP site and the recombination of alleles, specific primers and PCR protocols were designed and tested. The validation of this model will lead to further research on the role of this protein in bone mechanotransduction.

Supervisor: William R. Thompson, DPT, PhD 
Department: Physical Therapy