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Bcl‐2 regulates chondrocyte morphology and aggrecan gene expression independent of caspase activation and full apoptosis
Author(s) -
Feng Lixin,
Balakir Richard,
Precht Patricia,
Horton Walter E.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990915)74:4<576::aid-jcb7>3.0.co;2-n
Subject(s) - aggrecan , chondrocyte , apoptosis , microbiology and biotechnology , chemistry , biology , in vitro , medicine , biochemistry , pathology , osteoarthritis , alternative medicine , articular cartilage
Bcl‐2 is widely expressed in a variety of cell types and is known to block apoptosis through a conserved pathway. However, recent reports have demonstrated that Bcl‐2 regulates cell behavior independent of its control of apoptosis. Chondrocytes express a unique set of matrix proteins, including the proteoglycan aggrecan, and have been widely used to study the relationship between trophic factors and apoptosis. In this article, we report that Bcl‐2 affects the morphology and regulates the expression of aggrecan in a rat chondrocyte cell line (IRC). Endogenous Bcl‐2 and aggrecan mRNA were both down‐regulated in response to serum withdrawal in parental IRC cells, while constitutive expression of Bcl‐2 maintained aggrecan levels under conditions of serum withdrawal. In addition, expression of anti‐sense Bcl‐2 resulted in decreased aggrecan mRNA and produced a fibroblastic morphology compared with parental cells. The caspase inhibitor ZVAD‐fmk effectively blocked full apoptosis of IRC cells in response to serum withdrawal or anti‐sense Bcl‐2 but did not prevent the down‐regulation of aggrecan expression from either signal. These results suggest a novel role for Bcl‐2 in regulating the differentiated phenotype of chondrocytes and the expression of a differentiation‐specific gene independent of its control of apoptosis. J. Cell. Biochem. 74:576–586, 1999. © 1999 Wiley‐Liss, Inc.