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Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low
Robert Brommage1, Jeff Liu1, Deon Doree1
1Lexicon Pharmaceuticals , The Woodlands, TX, USA.
Abstract:
Disruption of serotonin synthesis in neurons and the periphery by knockout (KO) of mouse genes for tryptophan hydroxylases (peripheral Tph1 and neuronal Tph2) has been claimed to decrease (Tph2 KO) and increase (Tph1 KO) bone mass. In this report, adult male and female Tph2 KO mice were observed to have elevated spine trabecular bone. Female Tph2 KO mice have reduced midshaft femur cortical bone thickness. Bone mass was normal in male and female Tph1 KO mice examined as part of a Tph1/Tph2 double knockout (DKO) mouse cohort.
Insights
Altering serotonin production via tryptophan hydroxylase gene knockout affects bone mass differently in mice. Neuronal Tph2 knockout increases spine bone, while peripheral Tph1 knockout shows no bone mass changes.
Area of Science:
- Neuroscience
- Endocrinology
- Skeletal Biology
Background:
- Serotonin, a neurotransmitter, is synthesized via tryptophan hydroxylases (Tph1 and Tph2).
- Previous studies suggest Tph1 and Tph2 gene knockout (KO) differentially impact bone mass.
- The precise roles of neuronal Tph2 and peripheral Tph1 in bone metabolism require further elucidation.
Purpose of the Study:
- To investigate the effects of Tph2 and Tph1 gene disruption on bone mass in adult mice.
- To analyze the impact of neuronal and peripheral serotonin synthesis on trabecular and cortical bone.
Main Methods:
- Utilized knockout (KO) mouse models for Tph2 and Tph1 genes.
- Examined adult male and female mice from Tph2 KO and Tph1/Tph2 double knockout (DKO) cohorts.
- Assessed bone mass, focusing on spine trabecular bone and femur cortical bone thickness.
Main Results:
- Tph2 KO mice exhibited elevated spine trabecular bone in both sexes.
- Female Tph2 KO mice showed reduced midshaft femur cortical bone thickness.
- Bone mass remained normal in Tph1 KO mice within the DKO cohort.
Conclusions:
- Neuronal serotonin synthesis, regulated by Tph2, significantly influences bone mass, particularly in the spine.
- Peripheral serotonin synthesis, via Tph1, appears to have a limited role in regulating overall bone mass.
- These findings highlight the distinct contributions of central and peripheral serotonin pathways to skeletal homeostasis.
