Dexamethasone differentially regulates Bcl-2 family proteins in human proliferative chondrocytes: Role of pro-apoptotic Bid

Farasat Zaman, Dionisios Chrysis, Kirsten Huntjens, Andrei Chagin, Masaharu Takigawa, Bengt Fadeel, Lars Sävendahl

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Glucocorticoids (GCs) are widely used to treat inflammatory diseases and cancers. A multitude of undesired side effects have been reported in GC-treated patients including decreased linear bone growth. We have previously reported that GCs activate the caspase cascade and trigger Bax-mediated mitochondrial apoptosis in growth plate chondrocytes causing growth retardation in young mice. To further explore the role of mitochondrial apoptosis in GC-induced bone growth retardation, a number of pro- and anti-apoptotic proteins were studied in ex vivo cultures of human growth plate cartilage and human HCS-2/8 proliferative chondrocytes exposed to dexamethasone. Dexamethasone was found to increase the pro-apoptotic proteins Bcl-xS, Bad, and Bak as well as the proteolysis of Bid. Anti-Bid small interfering RNA partially rescued the chondrocytes from dexamethasone-induced apoptosis. Taken together, our data suggest that GC treatment differentially regulates Bcl-2 family member proteins to facilitate mitochondrial apoptosis in proliferative chondrocytes thereby contributing to GC-induced bone growth impairment. Prevention of this imbalance between pro- and anti-apoptotic Bcl-2 family proteins may provide a new strategy to protect from adverse effects of GCs on bone growth.

Original languageEnglish
Pages (from-to)196-200
Number of pages5
JournalToxicology Letters
Volume224
Issue number2
DOIs
Publication statusPublished - Jan 13 2014

Keywords

  • Apoptosis
  • Bcl-2 family proteins
  • Bid
  • Chondrocytes
  • Dexamethasone
  • Human growth plate

ASJC Scopus subject areas

  • Toxicology

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