Our research focuses on the role of the calpain small subunit in bone development and remodeling using genetically manipulated mouse models.
Parathyroid hormone (PTH) regulates blood calcium through actions mainly in bones and kidneys. PTH-related peptide (PTHrP), a locally released protein, primarily affects skeletal differentiation and organ development. Both PTH and PTHrP bind to the same receptor.
Calpains are enzymes consisting of a large subunit and a small subunit encoded by the gene Capns1 that cleave to various proteins to modulate their functions in cells. We established direct binding between the intracellular tail of the PTH/PTHrP receptor and the calpain small subunit, that is essential for embryonic survival and regulates calpains’ protease stability and activity.
Using genetically manipulated mouse models, our project has focused on investigating the role of the calpain small subunit in:
Publications during the last 5 years
1. Shimada, M. 2012. Overview of Calpain-Mediated Regulation of Bone and Fat Mass in Osteoblasts. Cell Biochem Biophys. 10.1007/s12013-012-9393-7. PMCID: PMC in progress.
2. Shimada, M. 2012 (in press). Calpain-mediated regulation of bone and fat mass and glucose homeostasis in osteoblasts. In: Adipocytes: Biology, Regulation, and Health Impact. Hauppauge (NY): Nova Science Publisher, Inc.
3. Kashiwagi A, Fein MJ, and Shimada M. 2011. Calpain modulates cyclin-dependent kinase inhibitor 1B (p27Kip1) in cells of the osteoblast lineage. Calcif. Tissue Int. 89(1): 36-42. PMCID: PMC3111891.
4. Kashiwagi A, Fein MJ, and Shimada M. 2011. A high fat diet-induced impaired glucose metabolism in mice with targeted deletion of calpain in osteoblasts. Biochem. Biophys. Res. Commun. 409(2): 235-40. PMCID: PMC3120767.
5. Kashiwagi A, Schipani E, Fein MJ, Greer PA, and Shimada M. 2010. Targeted Deletion of Capn4 in cells of the chondrocyte lineage impairs chondrocyte proliferation and differentiation. Mol. Cell. Biol. 30(11): 2799-2810. PMCID: PMC2876508.
6. Shimada, M. 2009. A Challenging Case of Severe Acute Hypertriglyceridemia-Induced Pancreatitis. South. Med. J. 102(10):999-1000.
7. Shimada M, Greer PA, McMahon AP, Bouxsein ML, and Schipani E. 2008. In vivo targeted deletion of calpain small subunit, Capn4, in cells of the osteoblast lineage impairs cell proliferation, differentiation, and bone formation. J Biol. Chem. 283(30): 21002-10. PMCID: PMC2475719
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