The role of transforming growth factor-beta on retarded osteoblastic differentiation in vitro.
Various matrix growth factors play important roles in the development and growth of cartilage and bone. Among them transforming growth factor-beta superfamily and especially bone morphogenetic proteins are known to be important factors, since they induce bone and cartilage formation in ectopic sites in vivo. We have previously shown that the human osteosarcoma cell line Saos-2 expresses molecules that in vivo induce new bone formation with asymmetric bone maturation. In this study we examined the role of Saos-2-conditioned medium in prolonged cultures of mesenchymal C3H/10T1/2 cells. The C3H/10T1/2 cells were cultured with Saos-2-conditioned medium for 28 days. We show that Saos-2-treated C3H/10T1/2 cells performed retarded osteoblastic differentiation when compared to recombinant BMP-2 and -4 induced differentiation. We further show that this retardation is due to excessive amounts of transforming growth factor-beta in Saos-2-conditioned medium. Our results also suggest that this model can well be used to study additional cofactors involved in retarded osteogenesis.
Laitinen
M
M
Institute of Medical Technology, University of Tampere and University Central Hospital of Tampere, Finland. laitinen_minna@hotmail.com
Halttunen
T
T
Jortikka
L
L
Teronen
O
O
Sorsa
T
T
Lindholm
T S
TS
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008648:Mesoderm; D051379:Mice; D008854:Microscopy, Electron; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin; D000469:Alkaline Phosphatase