Peripheral serotonin is synthesized by tryptophan hydroxylase-1 (TPH(1)). This study examined bone remodeling in TPH(1) knockout mice. The authors find that in the presence of RANKL, osteoclast precursors express TPH(1) and synthesize serotonin. Furthermore, pharmacological inhibition of serotonin receptor 1B with SB224289, and of receptor 2A with ketanserin, also reduced the number of osteoclasts. Bone resorption in TPH(1)(-/-) mice, as assessed by biochemical markers and bone histomorphometry, was markedly decreased. These findings demonstrate that serotonin amplifies the effect of RANKL on osteoclastogenesis.
Chabbi-Achengli Y, Coudert AE, Callebert J, Geoffroy V, Côté F, Collet C, de Vernejoul MC.