Abstract
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.
Highlights
Osteoblasts differentiate from bone marrow stromal cells (BMSCs), known as mesenchymal stem cells, which have the capacity to become adipocytes or fibroblasts [1]
These results indicated that bone marrow stromal antigen 2 (BST2) expression was significantly increased during the differentiation of hAD-BMSCs into osteoblasts
BST2 expression was continuously inhibited in cells treated with osteoblast-induction stimulants (OS) and either siBST2 #1 or #2 compared with cells treated with OS and non-targeting siRNA (Fig 1B). quantitative real-time PCR (qRT-PCR) data showed that BST2 mRNA expression was reduced in siBST2 #1 and #2 treated cells by approximately 74% and 63%, respectively, compared with cells treated with the control siRNA (Fig 1B)
Summary
Osteoblasts differentiate from bone marrow stromal cells (BMSCs), known as mesenchymal stem cells, which have the capacity to become adipocytes or fibroblasts [1]. Human alveolar-derived BMSCs (hAD-BMSCs) have been successfully isolated and cultured [2]. These cells may be useful for periodontal bone regenerative medicine because marrow blood can be aspirated from alveolar bone during tooth extraction and dental implant surgery [3, 4]. The bone morphogenetic protein (BMP) 2 signaling pathway is an essential regulator of osteogenesis. BMP2 binds to its receptors and activates SMADs, which directly regulate target gene expression [5]. RUNX 2 is a key transcription factor for osteogenesis [9], and regulates the expression of several osteoblastic genes including collagen type 1α (COL1α), bone sialoprotein (BSP) and the skeletal-specific osteocalcin (OCN) gene. We identified several differentially expressed genes, including bone marrow stromal antigen 2 (BST2)
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