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Serotonin and bone (C. Collet, M-C. de Vernejoul)

Besides its action as a neurotransmitter, serotonin has multiple physiological functions in several peripheral organs. Recently Yadav et al suggested that peripheral serotonin produced in the gut was a major negative regulator of osteoblast proliferation. However, we observed that low doses of serotonin stimulate osteoblast proliferation and that osteoblasts express a functional 2B serotonin receptor (5-HT2BR). Mice invalidated for the 5-HT2BR (5-HT2BR-/-), displayed reduced bone formation that got worse with age (Collet et al 2008). Moreover, we also demonstrated that serotonin was synthesized by osteoclasts (Chabbi-Achengli et al, 2012). Our results suggest that serotonin could be one of the paracrine and autocrine systems controlling bone formation. The importance of the serotonin system is due to the popular use of drugs targeting this system for the treatment of depression. Inhibitors of the serotonin transporter (SERT) were suggested to decrease bone formation and increase the occurrence of femoral neck fracture.

Considering these different points, the following interdependent objectives will be addressed:

1. What is the role of serotonin and/or of serotonin receptors and the serotonin transporter (SERT) on osteoblast proliferation and differentiation and are they interrelated

2. by which mechanism does the 5-HT2B R stimulate bone formation, and is it possible that this receptor has different features in bone than in other tissues; This project was funded by a grant to C Collet in 2012 (ECTS/Servier award).