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), β-glycerophosphate (GP), and dexamethasone (Dex). Bone morphogenic protein (BMP)-2 is an osteoinductive factor that can commit stromal cells to differentiate i...
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Published in | Development, growth & differentiation Vol. 50; no. 7; pp. 553 - 564 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Melbourne, Australia
Melbourne, Australia : Blackwell Publishing Asia
01.09.2008
Blackwell Publishing Asia |
Subjects | |
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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. |
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AbstractList | 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. 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. 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. 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. |
Author | Song, Yoon Mi Park, Yong Doo Noh, Insup Weber, Franz Cho, Tae Hyung Lee, Kyu Back Hwang, Soon Jung Kim, In Sook |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19238726$$D View this record in MEDLINE/PubMed |
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Snippet | 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... 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... A number of factors must be added to human bone marrow stromal cells (hBMSCs) in vitro to induce osteogenesis, including ascorbic acid (AA),... A number of factors must be added to human bone marrow stromal cells (hBMSCs) in vitro to induce osteogenesis, including ascorbic acid (AA), β... |
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SubjectTerms | 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 |
Title | 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 |
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