BoneKEy Reports | BoneKEy Watch

Mice that lack peripheral serotonin show reduced osteoclastogenesis

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DOI:10.1038/bonekey.2012.89

Production of peripheral serotonin in the gut was initially reported to decrease bone mass by inhibiting bone formation, but, subsequently, conflicting views have emerged, prompting this study using mice that lack the gene for tryptophan hydroxylase-1 (TPH1), the enzyme that synthesizes serotonin. The TPH1 knockout (KO) mice showed decreased bone resorption at maturity, and during growth, as measured using bone histomorphometry and biochemical marker turnover.

Further investigations revealed that this decrease in bone resorption was due to the mice having fewer osteoclasts, which had failed to differentiate from their precursors. This lower rate of differentiation could be reversed by supplying serotonin. The data also show that osteoclast precursors are stimulated to express TPH1, and so produce peripheral serotonin, if the receptor activator for the nuclear factor-KB ligand (RANKL) is present. The authors suggest this indicates that serotonin increases osteoclastogenesis by amplifying RANKL, and therefore has an important role in bone resorption.

Editor's comment: This careful analysis of TPH1 KO mice, which fail to produce peripheral serotonin, indicates that osteoclasts are the source of peripheral serotonin, which then activates bone resorption. Hence, peripheral serotonin production could be a therapeutic target in bone disease after all.

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