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Overview of Calpain-Mediated Regulation of Bone and Fat Mass in Osteoblasts

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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.

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Acknowledgments

This work was partially supported by the National Institutes of Health grants R01 DK072102 and P30 DK057521, the William F. Milton Fund, and the MGH interim support fund (to M. S.).

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Authors and Affiliations

  1. Endocrine Unit, Massachusetts General Hospital, Thier 10, 50 Blossom Street, Boston, MA, 02114, USA

    Masako Shimada

  2. Department of Medicine, Harvard Medical School, Boston, MA, 02114, USA

    Masako Shimada

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  1. Masako Shimada
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Correspondence to Masako Shimada.

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Shimada, M. Overview of Calpain-Mediated Regulation of Bone and Fat Mass in Osteoblasts. Cell Biochem Biophys 66, 23–28 (2013). https://doi.org/10.1007/s12013-012-9393-7

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  • DOI: https://doi.org/10.1007/s12013-012-9393-7

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