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

• Published in: Development, growth & differentiation Vol. 50; no. 7; pp. 553 - 564
• Main Authors: Kim, In Sook, Song, Yoon Mi, Cho, Tae Hyung, Park, Yong Doo, Lee, Kyu Back, Noh, Insup, Weber, Franz, Hwang, Soon Jung
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Melbourne, Australia : Blackwell Publishing Asia 01.09.2008; Blackwell Publishing Asia
• Subjects: Adolescent; Adult; alkaline phosphatase; Bone Marrow Cells - drug effects; Bone Marrow Cells - physiology; Bone Morphogenetic Protein 2 - pharmacology; Bone Morphogenetic Protein 2 - physiology; bone morphogenic protein-2; Cell Culture Techniques; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Female; human bone marrow stromal cells; Humans; in vitro matrix mineralization; Male; Middle Aged; osteoblast differentiation; Osteoblasts - drug effects; Osteoblasts - physiology; Recombinant Proteins - pharmacology; Stromal Cells - drug effects; Stromal Cells - physiology; Time Factors; Young Adult
• ISSN: 0012-1592; 1440-169X
• DOI: 10.1111/j.1440-169X.2008.01052.x

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.