PMID- 21277400
OWN - NLM
STAT- MEDLINE
DCOM- 20110811
LR  - 20131121
IS  - 1873-2763 (Electronic)
IS  - 1873-2763 (Linking)
VI  - 48
IP  - 5
DP  - 2011 May 1
TI  - The protective role of bone morphogenetic protein-8 in the glucocorticoid-induced 
      apoptosis on bone cells.
PG  - 1052-7
LID - 10.1016/j.bone.2011.01.017 [doi]
AB  - One of the side effects associated with glucocorticoid therapy is 
      glucocorticoid-induced bone loss. Glucocorticoids partly detain bone formation 
      via the inhibition of osteoblastic function, however, the exact mechanism of this 
      inhibition remains elusive. In this study, we examined the effect of 
      dexamethasone, an active glucocorticoid analogue, on cell viability and 
      expression of bone remodelling-related genes in primary mouse calvarial and 
      cloned MC3T3-E1 osteoblasts. Using sensitive biochemical assays, we demonstrated 
      the apoptotic effect of dexamethasone on osteoblastic cells. Then, utilizing 
      Taqman probe-based quantitative RT-PCR technology, gene expression profiles of 
      111 bone metabolism-related genes were determined. As a result of dexamethasone 
      treatment we have detected significant apoptotic cell death, and six genes, 
      including Smad3, type-2 collagen alpha-1, type-9 collagen alpha-1, matrix 
      metalloproteinase-2, bone morphogenetic protein-4 and bone morphogenetic 
      protein-8 showed (BMP-8) significant changes in their expression on a time- and 
      concentration-dependent manner. BMP-8, (a novel player in bone-metabolism) 
      exhibited a two orders of magnitude elevation in its mRNA level and highly 
      elevated protein concentration by Western blot in response to dexamethasone 
      treatment. The knockdown of BMP-8 by RNA interference significantly increased 
      dexamethasone-induced cell death, confirming a protective role for BMP-8 in the 
      glucocorticoid-induced apoptosis of osteoblasts. Our results suggest that BMP-8 
      might be an essential player in bone metabolism, especially in response to 
      glucocorticoids.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Kosa, Janos P
AU  - Kosa JP
AD  - 1st Department of Internal Medicine of Semmelweis University, Budapest, Hungary. 
      jkosa@bel1.sote.hu
FAU - Kis, Adrian
AU  - Kis A
FAU - Bacsi, Krisztian
AU  - Bacsi K
FAU - Balla, Bernadett
AU  - Balla B
FAU - Nagy, Zsolt
AU  - Nagy Z
FAU - Takacs, Istvan
AU  - Takacs I
FAU - Speer, Gabor
AU  - Speer G
FAU - Lakatos, Peter
AU  - Lakatos P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110127
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Small Interfering)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Biological Assay
MH  - Blotting, Western
MH  - Bone Morphogenetic Proteins/genetics/*metabolism
MH  - Caspase 3/metabolism
MH  - Caspase 7/metabolism
MH  - Cell Survival/drug effects
MH  - Cytoprotection/*drug effects
MH  - Dexamethasone/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/drug effects
MH  - Gene Knockdown Techniques
MH  - Glucocorticoids/*pharmacology
MH  - Mice
MH  - Osteoblasts/*cytology/*drug effects/enzymology
MH  - RNA, Small Interfering/metabolism
MH  - Skull/cytology
MH  - Time Factors
EDAT- 2011/02/01 06:00
MHDA- 2011/08/13 06:00
CRDT- 2011/02/01 06:00
PHST- 2010/11/03 00:00 [received]
PHST- 2011/01/05 00:00 [revised]
PHST- 2011/01/21 00:00 [accepted]
PHST- 2011/02/01 06:00 [entrez]
PHST- 2011/02/01 06:00 [pubmed]
PHST- 2011/08/13 06:00 [medline]
AID - S8756-3282(11)00021-4 [pii]
AID - 10.1016/j.bone.2011.01.017 [doi]
PST - ppublish
SO  - Bone. 2011 May 1;48(5):1052-7. doi: 10.1016/j.bone.2011.01.017. Epub 2011 Jan 27.