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


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.
Mehlhorn
A T
AT
Department of Orthopaedic and Trauma Surgery, University Medical Center Freiberg, Germany. alexander.mehlhorn@uniklinik-freiburg.de
Niemeyer
P
P
Kaschte
K
K
Muller
L
L
Finkenzeller
G
G
Hartl
D
D
Sudkamp
N P
NP
Schmal
H
H
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000328:Adult; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D024121:Collagen Type X; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D000469:Alkaline Phosphatase