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 language | English |
|---|---|
| Pages (from-to) | 196-200 |
| Number of pages | 5 |
| Journal | Toxicology Letters |
| Volume | 224 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 13 2014 |
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Keywords
- Apoptosis
- Bcl-2 family proteins
- Bid
- Chondrocytes
- Dexamethasone
- Human growth plate
ASJC Scopus subject areas
- Toxicology
Cite this
Dexamethasone differentially regulates Bcl-2 family proteins in human proliferative chondrocytes : Role of pro-apoptotic Bid. / Zaman, Farasat; Chrysis, Dionisios; Huntjens, Kirsten; Chagin, Andrei; Takigawa, Masaharu; Fadeel, Bengt; Sävendahl, Lars.
In: Toxicology Letters, Vol. 224, No. 2, 13.01.2014, p. 196-200.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dexamethasone differentially regulates Bcl-2 family proteins in human proliferative chondrocytes
T2 - Role of pro-apoptotic Bid
AU - Zaman, Farasat
AU - Chrysis, Dionisios
AU - Huntjens, Kirsten
AU - Chagin, Andrei
AU - Takigawa, Masaharu
AU - Fadeel, Bengt
AU - Sävendahl, Lars
PY - 2014/1/13
Y1 - 2014/1/13
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Bcl-2 family proteins
KW - Bid
KW - Chondrocytes
KW - Dexamethasone
KW - Human growth plate
UR - http://www.scopus.com/inward/record.url?scp=84888179402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888179402&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2013.10.020
DO - 10.1016/j.toxlet.2013.10.020
M3 - Article
C2 - 24172751
AN - SCOPUS:84888179402
VL - 224
SP - 196
EP - 200
JO - Toxicology Letters
JF - Toxicology Letters
SN - 0378-4274
IS - 2
ER -