Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells

A T Mehlhorn, P Niemeyer, K Kaschte, L Muller, G Finkenzeller, D Hartl, N P Sudkamp, H Schmal

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

OBJECTIVES: This article addresses the interaction of transforming growth factor beta1 (TGF-beta1) and bone morphogenic protein 2 (BMP-2) during osteo-chondrogenic differentiation of adipose-derived adult stem cells (ASC). TGF-beta1 was expected to modulate the BMP-2-induced effects through transcriptional regulation of Dlx-5, Msx-2 and Runx-2.

MATERIALS AND METHODS: Encapsulated ASC were cultured for 14 days in medium containing TGF-beta1 and/or BMP-2. mRNA expression of the extracellular matrix molecules col2a1, cartilage oligomeric matrix protein, col10a1, alkaline phosphatase (AP) and transcription factors Msx-2, Dlx-5 and Runx-2 was analysed. Release of glycosaminoglycans, collagen types II and X into the extracellular matrix was demonstrated.

RESULTS: BMP-2 and TGF-beta1 induced a chondrogenic phenotype in ASC. Combined growth factor treatment had a synergistic effect on col10a1 and an additive effect on col2a1 mRNA expression. Synthesis of glycosaminoglycans was enhanced by combined growth factor treatment. Addition of TGF-beta1 inhibited BMP-2 induced AP expression and activity and both proteins promoted chondrogenic maturation.

CONCLUSIONS: Prevention of BMP-2-induced osteogenic transdifferentiation by TGF-beta1 seemed not to be mediated by transcriptional regulation of Dlx-5. Due to these findings, simultaneous stimulation of ASC with BMP-2 and TGF-beta1 seemed to be beneficial for complete differentiation of ASC into chondrocytes.

OriginalsprogEngelsk
TidsskriftCell Proliferation
Vol/bind40
Udgave nummer6
Sider (fra-til)809-23
Antal sider15
ISSN0960-7722
DOI
StatusUdgivet - dec. 2007

Fingeraftryk

Transforming Growth Factor beta1
Proteins
Alkaline Phosphatase
Cartilage Oligomeric Matrix Protein
Collagen Type X
Messenger RNA
Collagen Type II
Chondrocytes

Citer dette

Mehlhorn, A T ; Niemeyer, P ; Kaschte, K ; Muller, L ; Finkenzeller, G ; Hartl, D ; Sudkamp, N P ; Schmal, H. / Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells. I: Cell Proliferation. 2007 ; Bind 40, Nr. 6. s. 809-23.
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title = "Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells",
abstract = "OBJECTIVES: This article addresses the interaction of transforming growth factor beta1 (TGF-beta1) and bone morphogenic protein 2 (BMP-2) during osteo-chondrogenic differentiation of adipose-derived adult stem cells (ASC). TGF-beta1 was expected to modulate the BMP-2-induced effects through transcriptional regulation of Dlx-5, Msx-2 and Runx-2.MATERIALS AND METHODS: Encapsulated ASC were cultured for 14 days in medium containing TGF-beta1 and/or BMP-2. mRNA expression of the extracellular matrix molecules col2a1, cartilage oligomeric matrix protein, col10a1, alkaline phosphatase (AP) and transcription factors Msx-2, Dlx-5 and Runx-2 was analysed. Release of glycosaminoglycans, collagen types II and X into the extracellular matrix was demonstrated.RESULTS: BMP-2 and TGF-beta1 induced a chondrogenic phenotype in ASC. Combined growth factor treatment had a synergistic effect on col10a1 and an additive effect on col2a1 mRNA expression. Synthesis of glycosaminoglycans was enhanced by combined growth factor treatment. Addition of TGF-beta1 inhibited BMP-2 induced AP expression and activity and both proteins promoted chondrogenic maturation.CONCLUSIONS: Prevention of BMP-2-induced osteogenic transdifferentiation by TGF-beta1 seemed not to be mediated by transcriptional regulation of Dlx-5. Due to these findings, simultaneous stimulation of ASC with BMP-2 and TGF-beta1 seemed to be beneficial for complete differentiation of ASC into chondrocytes.",
keywords = "Adipocytes, Adult, Alkaline Phosphatase, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins, Cell Differentiation, Chondrogenesis, Chondroitin Sulfates, Collagen Type II, Collagen Type X, Flow Cytometry, Gene Expression Regulation, Glycosaminoglycans, Humans, Hyaluronic Acid, RNA, Messenger, Stem Cells, Transforming Growth Factor beta, Transforming Growth Factor beta1, Journal Article",
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Mehlhorn, AT, Niemeyer, P, Kaschte, K, Muller, L, Finkenzeller, G, Hartl, D, Sudkamp, NP & Schmal, H 2007, 'Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells', Cell Proliferation, bind 40, nr. 6, s. 809-23. https://doi.org/10.1111/j.1365-2184.2007.00473.x

Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells. / Mehlhorn, A T; Niemeyer, P; Kaschte, K; Muller, L; Finkenzeller, G; Hartl, D; Sudkamp, N P; Schmal, H.

I: Cell Proliferation, Bind 40, Nr. 6, 12.2007, s. 809-23.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Differential effects of BMP-2 and TGF-beta1 on chondrogenic differentiation of adipose derived stem cells

AU - Mehlhorn, A T

AU - Niemeyer, P

AU - Kaschte, K

AU - Muller, L

AU - Finkenzeller, G

AU - Hartl, D

AU - Sudkamp, N P

AU - Schmal, H

PY - 2007/12

Y1 - 2007/12

N2 - OBJECTIVES: This article addresses the interaction of transforming growth factor beta1 (TGF-beta1) and bone morphogenic protein 2 (BMP-2) during osteo-chondrogenic differentiation of adipose-derived adult stem cells (ASC). TGF-beta1 was expected to modulate the BMP-2-induced effects through transcriptional regulation of Dlx-5, Msx-2 and Runx-2.MATERIALS AND METHODS: Encapsulated ASC were cultured for 14 days in medium containing TGF-beta1 and/or BMP-2. mRNA expression of the extracellular matrix molecules col2a1, cartilage oligomeric matrix protein, col10a1, alkaline phosphatase (AP) and transcription factors Msx-2, Dlx-5 and Runx-2 was analysed. Release of glycosaminoglycans, collagen types II and X into the extracellular matrix was demonstrated.RESULTS: BMP-2 and TGF-beta1 induced a chondrogenic phenotype in ASC. Combined growth factor treatment had a synergistic effect on col10a1 and an additive effect on col2a1 mRNA expression. Synthesis of glycosaminoglycans was enhanced by combined growth factor treatment. Addition of TGF-beta1 inhibited BMP-2 induced AP expression and activity and both proteins promoted chondrogenic maturation.CONCLUSIONS: Prevention of BMP-2-induced osteogenic transdifferentiation by TGF-beta1 seemed not to be mediated by transcriptional regulation of Dlx-5. Due to these findings, simultaneous stimulation of ASC with BMP-2 and TGF-beta1 seemed to be beneficial for complete differentiation of ASC into chondrocytes.

AB - OBJECTIVES: This article addresses the interaction of transforming growth factor beta1 (TGF-beta1) and bone morphogenic protein 2 (BMP-2) during osteo-chondrogenic differentiation of adipose-derived adult stem cells (ASC). TGF-beta1 was expected to modulate the BMP-2-induced effects through transcriptional regulation of Dlx-5, Msx-2 and Runx-2.MATERIALS AND METHODS: Encapsulated ASC were cultured for 14 days in medium containing TGF-beta1 and/or BMP-2. mRNA expression of the extracellular matrix molecules col2a1, cartilage oligomeric matrix protein, col10a1, alkaline phosphatase (AP) and transcription factors Msx-2, Dlx-5 and Runx-2 was analysed. Release of glycosaminoglycans, collagen types II and X into the extracellular matrix was demonstrated.RESULTS: BMP-2 and TGF-beta1 induced a chondrogenic phenotype in ASC. Combined growth factor treatment had a synergistic effect on col10a1 and an additive effect on col2a1 mRNA expression. Synthesis of glycosaminoglycans was enhanced by combined growth factor treatment. Addition of TGF-beta1 inhibited BMP-2 induced AP expression and activity and both proteins promoted chondrogenic maturation.CONCLUSIONS: Prevention of BMP-2-induced osteogenic transdifferentiation by TGF-beta1 seemed not to be mediated by transcriptional regulation of Dlx-5. Due to these findings, simultaneous stimulation of ASC with BMP-2 and TGF-beta1 seemed to be beneficial for complete differentiation of ASC into chondrocytes.

KW - Adipocytes

KW - Adult

KW - Alkaline Phosphatase

KW - Bone Morphogenetic Protein 2

KW - Bone Morphogenetic Proteins

KW - Cell Differentiation

KW - Chondrogenesis

KW - Chondroitin Sulfates

KW - Collagen Type II

KW - Collagen Type X

KW - Flow Cytometry

KW - Gene Expression Regulation

KW - Glycosaminoglycans

KW - Humans

KW - Hyaluronic Acid

KW - RNA, Messenger

KW - Stem Cells

KW - Transforming Growth Factor beta

KW - Transforming Growth Factor beta1

KW - Journal Article

U2 - 10.1111/j.1365-2184.2007.00473.x

DO - 10.1111/j.1365-2184.2007.00473.x

M3 - Journal article

VL - 40

SP - 809

EP - 823

JO - Cell Proliferation

JF - Cell Proliferation

SN - 0960-7722

IS - 6

ER -