Background Inhibitors of the SERT (SSRIs), the specific serotonin transporter, are efficient to treat depression. A decrease in bone formation has been reported in SERT-/- mice but their effects in bone remodelling are unclear. We have demonstrated that the osteoclast precursor needed serotonin to differentiate while SSRI Paroxetine was responsible for a decreased osteoclast differentiation.

Objectives We here aimed to study the bone phenotype and bone remodelling of SERT-/- mice in 129/Sv background, known to display an appropriate serotonin metabolism unlike C57BL/6J mice. The second aim was to evaluate the capacity of differentiation of precursors of bone cells in the absence of SERT.

Methods Bone histomorphometry was performed in 6 week-, 16 week- and 8 month-old SERT-/- mice. Ex vivo experiment analyses were conducted to assess the capacity of bone forming and resorbing cells from the bone marrow as well as the expression of differentiating factors.

Results Compared to WT mice, SERT-/- mice had a decreased bone formation as shown by a lower bone formation rate and lower level of P1NP at 6 weeks, 16 weeks and 8 months. At 6 weeks of age only, lower osteoclast number was counted at femur level and lower level of TRAP in SERT-/- mice as compared to WT mice, suggesting a diminished bone resorption in SERT-/-only in the postnatal period. Moreover, we found a decreased number of osteoclasts, osteoblasts and osteoprogenitors in SERT-/- primary cultures. These results were confirmed in primary cells derived from WT mice cultured in the presence of Paroxetine. Furthermore, SERT-/- osteoblasts had a lower expression of RANKL and a higher expression of OPG to WT osteoblasts. Also, a diminution of the ratio RANKL/OPG was observed in SERT-/-mice leading to a blunted osteoclast differentiation.

Conclusions Our results indicate that the SERT favors bone formation and resorption. The inhibition of SERT might therefore conduct to a low bone mass and promote the development of bone fragility.

Disclosure of Interest None declared