Podium 1: Skeletal Disorders, Treatments & Rehabilitation

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Age-Related Low Bone Mineral Density In C57Bl/6 Mice Is Reflective Of Aberrant Bone Morphogenetic Protein-2 Signaling Observed In Human Patients Diagnosed With Osteoporosis

Daniel Halloran, Presenter, Venu Pandit, Connor MacMurray, Victoria Stone, Kailey DeGeorge, Mark Eskander, Delaware Orthopaedic Specialists; Denise Root, Orthopedic Surgery, ChristianaCare Hospital; Sean McTague, Orthopedic Surgery, ChristianaCare Hospital; Heather Pelkey, Orthopedic Surgery, ChristianaCare Hospital; Anja Nohe, Principal Investigator

University of Delaware, ChristianaCare Hospital

Osteoporosis (OP) is a bone disorder characterized by decreased bone mineral density (BMD). Bone Morphogenetic Protein-2 (BMP-2) injections are used to promote bone formation in OP patients. However, patients are unresponsive to BMP-2 while displaying an upregulation of BMP Receptor Type 1a (BMPRIa) and protein kinase CK2? (CK2?). A synthetically produced peptide named casein kinase 2.3 (CK2.3) utilizes the BMP-signaling pathway as it enhances osteogenesis of primary osteoblasts isolated from OP patients, whereas BMP-2 does not. Although shown in OP patients, there is currently no reliable mouse model to study BMP-2 and CK2.3 signaling. In this publication, we show that BMPRIa was required for CK2.3-mediated osteogenesis in C2C12 cells with a CRISPR-Cas9-mediated gene knockout for BMPRIa. We utilized the C57BL/6 (B6) mouse strain as an aging-model to study aberrant BMP-2 signaling, demonstrating that, like OP patients, in 15 and 20-month mice, BMP-2 did not increase bone growth and displayed upregulated BMPRIa and CK2? protein expression. Furthermore, CK2.3 enhanced osteogenesis and decreased osteoclastogenesis in all age groups, whereas BMP-2 only increased mineralization in 6-month mice while increasing osteoclast formation in all age groups. These data demonstrated that aging B6 mice were a reliable model and mimicked data obtained from OP patients.

Research Area: Bone