Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo

Article


Owen, H., Ahmed, S. and Farquharson, C. 2009. Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo. Calcified Tissue International and Musculoskeletal Research. 85 (4), pp. 326-334. https://doi.org/10.1007/s00223-009-9276-0
TypeArticle
TitleChondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo
AuthorsOwen, H., Ahmed, S. and Farquharson, C.
Abstract

It has been shown that cell cycle genes play an important role in the coordination of chondrocyte proliferation and differentiation. The inhibitory effects of glucocorticoids (GCs) on chondrocyte proliferation are consistent with GCs disrupting cell cycle progression and promoting cell cycle exit. Cyclin-dependent kinase inhibitors (CDKIs) force cells to exit the cell cycle and differentiate, and studies have shown that expression of the CDKI p21(CIP1/WAF1) is increased in terminally differentiated cells. In this study, p21 mRNA and protein expression was increased during chondrocyte differentiation and after exposure to dexamethasone (Dex, 10(-6 )M) in murine chondrogenic ATDC5 cells. In 4-week-old mice lacking a functional p21 gene, Dex caused a reduction in body weight compared to saline control null mice, but this was consistent with the reduction in body weight observed in Dex-treated wild-type littermates. In addition, p21 ablation had no effect on the reduction in width of the growth plate or reduced mineral apposition rate in Dex-treated mice. However, an alteration in growth rate and epiphyseal structure is evident when comparing p21(-/-) and wild-type mice. These findings suggest that p21 does not directly contribute to GC-induced growth retardation in vivo but is involved in the maintenance of the growth plate.

Keywordsp21; Glucocorticoid; Dexamethasone; Growth plate; Chondrocyte; Growth retardation
PublisherSpringer
JournalCalcified Tissue International and Musculoskeletal Research
ISSN0171-967X
Electronic1432-0827
Publication dates
Print01 Oct 2009
Online01 Sep 2009
Publication process dates
Deposited21 Apr 2016
Accepted29 Jul 2009
Submitted30 Apr 2009
Output statusPublished
Digital Object Identifier (DOI)https://doi.org/10.1007/s00223-009-9276-0
Web of Science identifierWOS:000270647400007
LanguageEnglish
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