Lipopeptide Activation of TGF-ß1 Modulates Bone Remodelling in Osteoblasts 2D-Culture

Objectives: The aim of our research is to elaborate new fonctionnalized biomaterials in order to favour biological integration of implants or tissue regeneration. So, it was interesting to study one lipopeptide able to activate latent TGF-ß1, growth factor implicated in bone remodeling. Methods:This lipopeptide named elaïdyl-KRFK (Ea-KRFK) is composed of a fatty acid part : elaïdic acid covalently linked to a peptidic part, the KRFK tetrapeptide derived from type 1 Thrombospondin. During 24 hours, human osteoblasts were cultured in 24-wells plate at 100000 cells per well in the presence or not of this lipopeptide (5 µM) associated or not to exogenous latent TGF-ß1 (3 ng/ml). Results: The activation of exogenous latent TGF-ß1 by Ea-KRFK stimulates osteoblasts phenotype. The cell proliferation was enhanced by EA-KRFK with latent TGF-ß1. By RT-PCR, in the presence of Ea-KRFK associated to latent TGF-ß1, we observed an increase of osteopontin and alkaline phosphatase expression at 24 hours. By RT-PCR and ELISA technique, matrix metalloproteinases (MMPs)-1 and -3 and TIMPs-1 and -2 expression enhanced also after cells treatment by Ea-KRFK and latent TGF-ß1. These results were comparable to these obtained with alone active TGF-ß1. Alone, Ea-KRFK has few effects on protein expression by human osteoblasts. Its action was nearby of this obtained with control. Conclusions: Here, we showed that Ea-KRFK could partially reproduce the effects of active TGF-ß1 when it was associated with exogenous latent TGF-ß1 and stimulate osteoblast phenotype. It would be interesting to study the effect of this lipopeptide on osteoblast culture at long time to know its influence on bone mineralization.