RRC ID 19627
Author Owen HC, Ahmed SF, Farquharson C.
Title Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo.
Journal Calcif Tissue Int
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.
Volume 85(4)
Pages 326-34
Published 2009-10
DOI 10.1007/s00223-009-9276-0
PMID 19727539
MeSH Animals Body Weight Bone Density / drug effects Cell Cycle / drug effects Cell Differentiation / drug effects Cell Line Cell Proliferation / drug effects Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism* Cyclin-Dependent Kinase Inhibitor p21 / genetics Cyclin-Dependent Kinase Inhibitor p21 / metabolism* Dexamethasone / adverse effects Dexamethasone / pharmacology* Disease Models, Animal Female Glucocorticoids / adverse effects Glucocorticoids / pharmacology* Growth Disorders / chemically induced Growth Disorders / metabolism* Mice Mice, Knockout
IF 3.265
Times Cited 14
Human and Animal Cells ATDC5 (RCB0565)