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Mice lacking the calcineurin enhibitor Rcan2 have an isolated defect of osteoblast function.

Abstract

Calcineurin-NFAT signaling controls the differentiation and function of osteoclasts and osteoblasts, and regulator of calcineurin-2 (Rcan2) is a physiological inhibitor of this pathway. Rcan2 expression is regulated by 3,5,3'-L-triiodothyronine (T3), which also has a central role in skeletal development and bone turnover. To investigate the role of Rcan2 in bone development and maintenance, we characterized Rcan2-/- mice and determined its skeletal expression in T3 receptor (TR) knockout and thyroid manipulated mice. Rcan2-/- mice had normal linear growth but displayed delayed intramembranous ossification, impaired cortical bone formation and reduced bone mineral accrual during development as well as increased mineralization of adult bone. These abnormalities resulted from an isolated defect in osteoblast function and are similar to skeletal phenotypes of mice lacking the type 2 deiodinase thyroid hormone activating enzyme or with dominant negative mutations of TR?, the predominant TR isoform in bone. Rcan2 mRNA was expressed in primary osteoclasts and osteoblasts and its expression in bone was differentially regulated in TR? and TR? knockout and thyroid manipulated mice. However, in primary osteoblast cultures T3 treatment did not affect Rcan2 mRNA expression or NFATc1 expression and phosphorylation. Overall, these studies establish that Rcan2 regulates osteoblast function and its expression in bone is regulated by thyroid status in vivo.

Type Journal
Authors Bassett, J.H.D.; Logan, J.G.; Boyde, A.; Cheung, M.S.; Evans, H.; Croucher, P.; Sun, X.; Xu, S.; Murata, Y.; Williams, G.R.
Garvan Authors Prof Peter Croucher
Publisher Name ENDOCRINOLOGY
Published Date 2012-01-01 00:00:00
Published Volume 153
Published Issue 7
Published Pages 3537-48
URL http://www.ncbi.nlm.nih.gov/pubmed/22593270
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11398_11998/12 Bassett Endocrin_.pdf