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
| Autor: | Daniel Halloran, Venu Pandit, Connor MacMurray, Victoria Stone, Kailey DeGeorge, Mark Eskander, Denise Root, Sean McTague, Heather Pelkey, Anja Nohe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Osteoblasts
Organic Chemistry Bone Morphogenetic Protein 2 General Medicine Bone Morphogenetic Protein Receptors Catalysis Computer Science Applications Inorganic Chemistry Mice Inbred C57BL Mice Osteogenesis Animals Humans Osteoporosis Physical and Theoretical Chemistry osteoporosis osteoblasts osteoclasts C2C12 cells CK2 CK2.3 BMP-2 C57BL/6 mice Casein Kinase II Molecular Biology Spectroscopy Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 11205 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms231911205 |
| Popis: | 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 CK2α (CK2α). 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 CK2α 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. |
| Databáze: | OpenAIRE |
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