In vitro response of primary human bone marrow stromal cells to recombinant human bone morphogenic protein-2 in the early and late stages of osteoblast differentiation

In Sook Kim, Yoon Mi Song, Tae Hyung Cho, Yongdoo Park, Kyu Back Lee, Insup Noh, Franz Weber, Soon Jung Hwang

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

A number of factors must be added to human bone marrow stromal cells (hBMSCs) in vitro to induce osteogenesis, including ascorbic acid (AA), β-glycerophosphate (GP), and dexamethasone (Dex). Bone morphogenic protein (BMP)-2 is an osteoinductive factor that can commit stromal cells to differentiate into osteoblasts. However, it is still not clear whether the addition of BMP-2 alone in vitro can induce hBMSCs to complete osteoblast differentiation, resulting in matrix mineralization. This study compares the effects of BMP-2 and Dex, alone and combined, on the early and late stages of hBMSC differentiation. We found that BMP-2 causes a significant induction of alkaline phosphatase (ALP) activity in hBMSCs, with a transcriptional upregulation of known BMP-2-responsive genes, and the stable expression of cbfa1 in the nucleus and the regions surrounding the nucleus in the early phase of osteoblast differentiation. However, continuous treatment with BMP-2 alone at doses ranging from 100 to 300 ng/mL results in a less efficient enhancement of in vitro matrix mineralization, despite a significant induction of ALP activity at a concentration of 100 ng/mL. Our results reflect how the effects of BMP-2 on hBMSCs can vary depending on the stage of osteoblast differentiation, and highlight the need to understand the role of BMP-2 in primary hBMSCs derived from diverse sources in order to increase the efficiency of using BMP-2 in osteoinductive therapies.

Original languageEnglish
Pages (from-to)553-564
Number of pages12
JournalDevelopment Growth and Differentiation
Volume50
Issue number7
DOIs
Publication statusPublished - 2008 Sep 1

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Keywords

  • Alkaline phosphatase
  • Bone morphogenic protein-2
  • Human bone marrow stromal cells
  • In vitro matrix mineralization
  • Osteoblast differentiation

ASJC Scopus subject areas

  • Anatomy
  • Developmental Biology
  • Cell Biology

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