TGF-β1 on induced osteogenic differentiation of human dermal fibroblast

Abstract

PURPOSE:To evaluate the role of transforming growth factor beta 1 (TGF-β1) on the induced osteogenic differentiation of human dermal fibroblasts. METHODS:We performed four groups with cultured dermal fibroblasts according to the culture medium: CONTROL (DMEM culture medium); TGF-β1 (DMEM culture medium with 10 ng/ml of TGF-β1); OSTEOG (DMEM culture medium with 0.5 µg/ml of ascorbic acid, 10 mmol/l of β-glycerophosphate and 10 nmol/L of dexamethasone); and OSTEOG/TGF-β1 (osteogenic medium with 10 ng/ml of TGF-β1). Alkaline phosphatase (ALP) activity and the amount of osteocalcin (OC) in the supernatant, as well as the capability to form calcium phosphate deposits, were analysed for 28 days RESULTS: There were significant differences (p<0.05) between CONTROL and TGF-β1 groups in comparison with OSTEOG and OSTEOG/TGF-β1 groups in the ALP activity and OC amount. Although, both osteogenic groups had the same behavior with regard the expression curve during the experimental time, the OSTEOG/TGF-β1 group achieved significantly higher ALP and OC levels and showed no significant difference in the levels of mineralized deposits and in comparison with the levels found in the OSTEOG group. CONCLUSION:The addition of transforming growth factor beta 1 to the osteogenic culture medium increased the activity of alkaline phosphatase and the amount of osteocalcin, but TGF-β1 did not alter the presence of mineralized calcium phosphate deposits.

Human Fibroblasts as a Model for the Study of Bone Disorders

“…Interestingly, the stimulation of osteoblastogenesis by ALK5 inhibition is the opposite of what we observed in our study with the different ALK5 inhibitor GW788388 (13). In another study, the addition of TGF-β to osteogenic media was shown to improve the capacity of dermal fibroblasts for osteogenic transdifferentiation, although it did not contribute to mineralization (18). These differences may be attributed to the different growth factor compositions between these models, as well as to the different properties of the chemical inhibitors; for example, GW788388 is known to additionally target ALK4 and ALK7, which are TGF-β type I receptors for activin signaling (59).…”

Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress

“…In another approach, the subcutaneous ectopic bone formation in mice after implantation of the epigenetically modified fibroblasts [ 10 ]. Further, differentiation of fibroblasts toward the osteoblast lineage was also demonstrated with treatment of osteoclast-conditioned media, and TGF-β was shown to improve the capacity of fibroblasts for osteogenic differentiation [ 11 , 12 ]. The similarities of fibroblasts and mesenchymal stem cells support the use of fibroblasts as an appropriate cell type to study osteogenesis [ 13 ].…”

Inhibition of transforming growth factor‐β signaling pathway enhances the osteogenic differentiation of unrestricted somatic stem cells

“…TGF‐β1 contradictorily affects osteogenesis; while some researchers have shown that TGF‐β1 induces osteogenesis, either alone or together with other members of the family, such as BMP, in vivo and in vitro, others showed that TGF‐β1 had inhibitory effects on osteogenic markers such as alkaline phosphatase in mesenchymal stem cells . The variable effects of TGF‐β1 on osteogenesis appear to be dose or stage dependent .…”