The protective role of bone morphogenetic protein-8 in the glucocorticoid-induced apoptosis on bone cells

J. Kósa, Adrián Kis, Krisztián Bácsi, Bernadett Balla, Zsolt Nagy, I. Takács, G. Speer, P. Lakatos

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 α-1, type-9 collagen α-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.

Original languageEnglish
Pages (from-to)1052-1057
Number of pages6
JournalBone
Volume48
Issue number5
DOIs
Publication statusPublished - May 1 2011

Fingerprint

Bone Morphogenetic Proteins
Glucocorticoids
Dexamethasone
Apoptosis
Bone and Bones
Collagen Type IX
Osteoblasts
Cell Death
Bone Morphogenetic Protein 4
Genes
Collagen Type II
Bone Remodeling
Matrix Metalloproteinase 2
RNA Interference
Transcriptome
Osteogenesis
Cell Survival
Western Blotting
Technology
Polymerase Chain Reaction

Keywords

  • BMP-8
  • Calvarial osteoblast
  • Glucocorticoid-induced osteoporosis
  • MC3T3-E1
  • SiRNA
  • Transcriptional profiling

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

The protective role of bone morphogenetic protein-8 in the glucocorticoid-induced apoptosis on bone cells. / Kósa, J.; Kis, Adrián; Bácsi, Krisztián; Balla, Bernadett; Nagy, Zsolt; Takács, I.; Speer, G.; Lakatos, P.

In: Bone, Vol. 48, No. 5, 01.05.2011, p. 1052-1057.

Research output: Contribution to journalArticle

Kósa, J. ; Kis, Adrián ; Bácsi, Krisztián ; Balla, Bernadett ; Nagy, Zsolt ; Takács, I. ; Speer, G. ; Lakatos, P. / The protective role of bone morphogenetic protein-8 in the glucocorticoid-induced apoptosis on bone cells. In: Bone. 2011 ; Vol. 48, No. 5. pp. 1052-1057.
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