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.
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.
Kim
In Sook
IS
Dental Research Institute, Seoul National University, Brain Korea 21 2nd Program for Craniomaxillofacial Life Science, Seoul 110-749, Korea.
Song
Yoon Mi
YM
Cho
Tae Hyung
TH
Park
Yong Doo
YD
Lee
Kyu Back
KB
Noh
Insup
I
Weber
Franz
F
Hwang
Soon Jung
SJ
D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology* / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D055815:Young Adult
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins