Le CLCF1 inhibe la différenciation des MSC en ostéoblastes
Mesenchymal stem cells (MSC) are multipotent cells capable of differentiating into adipocytes, chondrocytes, osteocytes or myocytes. They are present in most tissues in adults and fetuses. MSC secrete an array of cytokines giving them the ability to regulate immune responses. MSC have immunosuppressive properties and were therefore tested in clinical trials. MSC express the leukemia inhibitory factor receptor chain (LIFRβ) on their surface. A mutation in the LIFR gene is associated with the Stüve-Wiedemann syndrome characterised by the development of scoliosis, curvatures of the long bones and the inability to regulate body temperature. LIFRβ is one of the signalling chains of the cardiotrophin-like cytokine (CLCF1) receptor. We therefore tested the hypothesis that CLCF1 regulates the differentiation of MSC into osteoblasts. Preliminary results showed that CLCF1 binds bone marrow-derived MSC as well as a bone marrow population that is negative for the hematopoietic cell marker CD45. The addition of CLCF1 during the induction of MSC differentiation into osteoblasts resulted in a decrease in alkaline phosphatase activity and in mineralization. Analysis of mARN levels by RT-qPCR indicated that the inhibitory effect of CLCF1 on osteoblast differentiation was paralleled by a down-regulation of the expression of Runx2, Osterix and Dlx5, 3 transcription factors involved in the control of osteogenesis. In conclusion, these results suggest that CLCF1 inhibits the differentiation of MSC into osteoblasts and that this cytokine is a potential therapeutic target in bone pathologies such as osteoporosis.
Cytokines CLCF1 LIFR Mesenchymal stem cells Cytokines Osteoblast