BST2 Mediates Osteoblast Differentiation via the BMP2 Signaling Pathway in Human Alveolar-Derived Bone Marrow Stromal Cells

The molecular mechanisms controlling the differentiation of bone marrow stromal stem cells into osteoblasts remain largely unknown. In this study, we investigated whether bone marrow stromal antigen 2 (BST2) influences differentiation toward the osteoblasts lineage. BST2 mRNA expression in human alv...

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Bibliographic Details
Published in:PloS one 2016-06, Vol.11 (6), p.e0158481-e0158481
Main Authors: Yoo, Su-Hyang, Kim, Jae Goo, Kim, Beom-Su, Lee, Jun, Pi, Sung-Hee, Lim, Hyun-Dae, Shin, Hong-In, Cho, Eui-Sic, You, Hyung-Keun
Format: Article
Language:English
Subjects:
Alkaline phosphatase
Alveolar bone
Antigens
Antigens, CD - physiology
B cells
Biocompatibility
Biodiversity
Biology and Life Sciences
Bone marrow
Bone Marrow Cells - drug effects
Bone Marrow Cells - physiology
Bone morphogenetic protein 2
Bone Morphogenetic Protein 2 - physiology
Bone morphogenetic proteins
Bone sialoprotein
Cancer
Cbfa-1 protein
Cell Differentiation - drug effects
Cell Differentiation - genetics
Cells, Cultured
Collagen
Dentistry
Deoxyribonucleic acid
Differentiation (biology)
DNA
Fibroblasts
Gene expression
Gene Expression Regulation - drug effects
Genomics
GPI-Linked Proteins - antagonists & inhibitors
GPI-Linked Proteins - physiology
Homeostasis
Humans
Medicine and Health Sciences
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - physiology
Middle Aged
Molecular modelling
Osteoblastogenesis
Osteoblasts
Osteoblasts - drug effects
Osteoblasts - physiology
Osteocalcin
Osteogenesis - drug effects
Osteogenesis - genetics
Phosphatases
Phosphorylation
Proteins
Receptors
Research and Analysis Methods
RNA
RNA, Small Interfering - pharmacology
Signal transduction
Signal Transduction - drug effects
Signal Transduction - genetics
Signaling
siRNA
Smad4 protein
Stem cells
Stromal cells
Surgery
Transcription factors
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Summary:The molecular mechanisms controlling the differentiation of bone marrow stromal stem cells into osteoblasts remain largely unknown. In this study, we investigated whether bone marrow stromal antigen 2 (BST2) influences differentiation toward the osteoblasts lineage. BST2 mRNA expression in human alveolar-derived bone marrow stromal cells (hAD-BMSCs) increased during differentiation into osteoblasts. hAD-BMSCs differentiation into osteoblasts and the mRNA expression of the bone-specific markers alkaline phosphatase, collagen type α 1, bone sialoprotein, osteocalcin, and osterix were reduced by BST2 knockdown using siRNA. Furthermore, BST2 knockdown in hAD-BMSCs resulted in decreased RUNX2 mRNA and protein expression. We hypothesized that BST2 is involved in differentiation of into osteoblasts via the BMP2 signaling pathway. Accordingly, we evaluated the mRNA expression levels of BMP2, BMP receptors (BMPR1 and 2), and the downstream signaling molecules SMAD1, SMAD4, and p-SMAD1/5/8 in BST2 knockdown cells. BMP2 expression following the induction of differentiation was significantly lower in BST2 knockdown cells than in cells treated with a non-targeting control siRNA. Similar results were found for the knockdown of the BMP2 receptor- BMPR1A. We also identified significantly lower expression of SMAD1, SMAD4, and p-SMAD1/5/8 in the BST2 knockdown cells than control cells. Our data provide the first evidence that BST2 is involved in the osteogenic differentiation of bone marrow stromal cells via the regulation of the BMP2 signaling pathway.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0158481