CCN2/CTGF is required for matrix organization and to protect growth plate chondrocytes from cellular stress

CCN2/CTGF is required for matrix organization and to protect growth plate chondrocytes from cellular stress

CCN2 (connective tissue growth factor (CTGF/CCN2)) is a matricellular protein that utilizes integrins to regulate cell proliferation, migration and survival. The loss of CCN2 leads to perinatal lethality resulting from a severe chondrodysplasia. Upon closer inspection of Ccn2 mutant mice, we observe...

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Bibliographic Details
Published in:Journal of cell communication and signaling Vol. 7; no. 3; pp. 219 - 230
Main Authors: Hall-Glenn, Faith, Aivazi, Armen, Akopyan, Lusi, Ong, Jessica R., Baxter, Ruth R., Benya, Paul D., Goldschmeding, Roel, van Nieuwenhoven, Frans A., Hunziker, Ernst B., Lyons, Karen M.
Format: Journal Article
Language:English
Published: Dordrecht Springer Netherlands 01-08-2013
John Wiley & Sons, Inc
Subjects:
Autophagy
Biomedical and Life Sciences
Biomedicine
Cartilage
CCN2/CTGF
Cell Biology
Cell proliferation
Cell survival
Cellular stress
Cellular stress response
Chondrocytes
Chondrodystrophy
Connective tissue growth factor
Extracellular matrix
Growth plate
Immunofluorescence
Integrins
Lethality
Life Sciences
NF-κB protein
Nuclear factor κB
Phagocytosis
Research Article
Rodents
Survival
Transgenic mice
Cartilage
Cellular stress
CCN2/CTGF
Autophagy
Chondrocytes
Nuclear factor κB
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Summary:CCN2 (connective tissue growth factor (CTGF/CCN2)) is a matricellular protein that utilizes integrins to regulate cell proliferation, migration and survival. The loss of CCN2 leads to perinatal lethality resulting from a severe chondrodysplasia. Upon closer inspection of Ccn2 mutant mice, we observed defects in extracellular matrix (ECM) organization and hypothesized that the severe chondrodysplasia caused by loss of CCN2 might be associated with defective chondrocyte survival. Ccn2 mutant growth plate chondrocytes exhibited enlarged endoplasmic reticula (ER), suggesting cellular stress. Immunofluorescence analysis confirmed elevated stress in Ccn2 mutants, with reduced stress observed in Ccn2 overexpressing transgenic mice. In vitro studies revealed that Ccn2 is a stress responsive gene in chondrocytes. The elevated stress observed in Ccn2 −/− chondrocytes is direct and mediated in part through integrin α5. The expression of the survival marker NFκB and components of the autophagy pathway were decreased in Ccn2 mutant growth plates, suggesting that CCN2 may be involved in mediating chondrocyte survival. These data demonstrate that absence of a matricellular protein can result in increased cellular stress and highlight a novel protective role for CCN2 in chondrocyte survival. The severe chondrodysplasia caused by the loss of CCN2 may be due to increased chondrocyte stress and defective activation of autophagy pathways, leading to decreased cellular survival. These effects may be mediated through nuclear factor κB (NFκB) as part of a CCN2/integrin/NFκB signaling cascade.
Bibliography:Electronic supplementary material
10.1007/s12079‐013‐0201‐y
The online version of this article (doi
contains supplementary material, which is available to authorized users.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1873-9601
1873-961X
DOI:10.1007/s12079-013-0201-y