Decreased osteoclastogenesis in serotonin-deficient mice.
Peripheral serotonin, synthesized by tryptophan hydroxylase-1 (TPH(1)), has been shown to play a key role in several physiological functions. Recently, controversy has emerged about whether peripheral serotonin has any effect on bone density and remodeling.We therefore decided to investigate in detail bone remodeling in growing and mature TPH(1) knockout mice (TPH(1)(-/-)). Bone resorption in TPH(1)(-/-) mice, as assessed by biochemical markers and bone histomorphometry, was markedly decreased at both ages. Using bone marrow transplantation, we present evidence that the decrease in bone resorption in TPH(1)(-/-) mice is cell-autonomous. Cultures from TPH(1)(-/-) in the presence of macrophage colony-stimulating factor and receptor activator for NF-KB ligand (RANKL) displayed fewer osteoclasts, and the decreased differentiation could be rescued by adding serotonin. Our data also provide evidence 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. Our findings reveal that serotonin has an important local action in bone, as it can amplify the effect of RANKL on osteoclastogenesis.
Institut National de la Santé et de la Recherche Médicale U606,  Hôpital Lariboisière, 75010 Paris,  France.
Yasmine
Y
Chabbi-Achengli
Amélie E
AE
Coudert
Jacques
J
Callebert
Valérie
V
Geoffroy
Francine
F
Côté
Corinne
C
Collet
Marie-Christine
MC
de Vernejoul
D000818:Animals; D002454:Cell Differentiation; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology*; D012701:Serotonin / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D012701:Serotonin; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase