Header

UZH-Logo

Maintenance Infos

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


Kim, I S; Song, Y M; Cho, T H; Park, Y D; Lee, K B; Noh, I; Weber, Franz E; Hwang, S J (2008). 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. Development, Growth and Differentiation, 50(7):553-564.

Abstract

A number of factors must be added to human bone marrow stromal cells (hBMSCs) in vitro to induce osteogenesis, including ascorbic acid (AA), beta-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.

Abstract

A number of factors must be added to human bone marrow stromal cells (hBMSCs) in vitro to induce osteogenesis, including ascorbic acid (AA), beta-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.

Statistics

Citations

36 citations in Web of Science®
44 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

69 downloads since deposited on 18 Nov 2008
9 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Clinic for Cranio-Maxillofacial Surgery
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:4 July 2008
Deposited On:18 Nov 2008 08:31
Last Modified:05 Oct 2017 12:19
Publisher:Wiley-Blackwell
ISSN:0012-1592
Additional Information:The attached file is a preprint (accepted version) of an article published in Development, Growth and Differentiation 2008,50(7),553-564.
Publisher DOI:https://doi.org/10.1111/j.1440-169X.2008.01052.x
PubMed ID:18616751

Download