Abstract
We have previously shown that human bone cells express bone morphogenetic protein receptor-IB (BMPR-IB). However, little is known about the precise role of this receptor in the response of osteoblastic genes to the BMP in these cells. To determine BMPR-IB-dependent osteoblastic gene expression, the present study examined the effects of BMPR-IB knockdown on BMP-induced osteoblast-associated genes. BMPR-IB mRNA and protein were markedly suppressed by transfection of cells with BMPR-IB siRNA. Using three different bone cell samples, BMP-2 stimulation of alkaline phosphatase (ALP), osteocalcin (OC), distal-less homeobox-5 (Dlx5) and core binding factor alpha-1 (Cbfa1) was found to be specifically and significantly reduced in the BMPR-IB siRNA-transfected cultures compared with that of control cultures. Our study has provided evidence that BMPR-IB-dependent signaling plays a crucial role in BMP-2 up-regulation of the ALP, OC, Dlx5 and Cbfa1 genes in bone cells, suggesting a pivotal role of this receptor in BMP-2-induced osteoblast differentiation in vitro. These findings thus suggest the possibility that BMPR-IB could be a therapeutic target for enhancing bone regeneration in vivo.
Original language | English |
---|---|
Pages (from-to) | 1362-1370 |
Number of pages | 0 |
Journal | Cell Biol Int |
Volume | 32 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2008 |
Keywords
- Alkaline Phosphatase
- Bone Development
- Bone Morphogenetic Protein 2
- Bone Morphogenetic Protein Receptors
- Type I
- Bone Regeneration
- Cell Differentiation
- Cells
- Cultured
- Core Binding Factor Alpha 1 Subunit
- Down-Regulation
- Gene Expression Regulation
- Developmental
- Homeodomain Proteins
- Humans
- Osteoblasts
- Osteocalcin
- Osteogenesis
- RNA Interference
- RNA
- Messenger
- Small Interfering
- Transcription Factors
- Transfection
- Up-Regulation