title: Overview of calpain-mediated regulation of bone and fat mass in osteoblasts.
abstract: The receptor for parathyroid hormone (PTH) and PTH-related peptide (PTH1R) belongs to the class II G protein-coupled receptor superfamily. The calpain small subunit encoded by the gene Capns1 is the second protein and the first enzyme identified by a yeast two-hybrid screen using the intracellular C-terminal tail of the rat PTH1R. The calpain regulatory small subunit forms a heterodimer with the calpain large catalytic subunit and modulates various cellular functions as a cysteine protease. To investigate a physiological role of the calpain small subunit in cells of the osteoblast lineage, we generated osteoblast-specific Capns1 knockout mouse models and characterized their bone phenotype. Molecular mechanisms by which calpain modulates cell proliferation of the osteoblast lineage were further examined in vitro. Moreover, we utilized the mutant mice as a disease model of osteoporosis accompanied with impaired bone resorptive function and suggested a possible clinical translation of our basic research finding.
authors: Endocrine Unit, Massachusetts General Hospital, Thier 10, 50 Blossom Street, Boston, MA 02114, USA. shimada@helix.mgh.harvard.edu
authors: Masako
authors: M
authors: Shimada
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis; D011401:Promoter Regions, Genetic; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain
chemical_list: C493961:Cdkn1b protein, mouse; D044168:Receptor, Parathyroid Hormone, Type 1; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D015675:Osteocalcin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002154:Calpain; C410233:Capns1 protein, mouse