論文 - 詳細
| RRC ID | 87270 |
|---|---|
| 著者 | Luo N, Mosialou I, Capulli M, Bisikirska B, Lin CS, Huang YY, Shyu PT, Guo XE, Economides A, Mann JJ, Kousteni S. |
| タイトル | A neuronal action of sirtuin 1 suppresses bone mass in young and aging mice. |
| ジャーナル | J Clin Invest |
| Abstract |
The various functions of the skeleton are influenced by extracellular cues, hormones, and neurotransmitters. One type of neuronal regulation favors bone mass accrual by inhibiting sympathetic nervous system (SNS) activity. This observation raises questions about the transcriptional mechanisms regulating catecholamine synthesis. Using a combination of genetic and pharmacological studies, we found that the histone deacetylase sirtuin 1 (SIRT1) is a transcriptional modulator of the neuronal control of bone mass. Neuronal SIRT1 reduced bone mass by increasing SNS signaling. SIRT1 did so by increasing expression of monoamine oxidase A (MAO-A), a SIRT1 target that reduces brain serotonin levels by inducing its catabolism and by suppressing tryptophan hydroxylase 2 (Tph2) expression and serotonin synthesis in the brain stem. SIRT1 upregulated brain catecholamine synthesis indirectly through serotonin, but did not directly affect dopamine β hydroxylase (Dbh) expression in the locus coeruleus. These results help us to understand skeletal changes associated with selective serotonin reuptake inhibitors (SSRIs) and may have implications for treating skeletal and metabolic diseases. |
| 巻・号 | 132(23) |
| 公開日 | 2022-12-1 |
| DOI | 10.1172/JCI152868 |
| PII | 152868 |
| PMID | 36194488 |
| PMC | PMC9711874 |
| MeSH | Aging* / genetics Animals Catecholamines Mice Monoamine Oxidase / genetics Monoamine Oxidase / metabolism Serotonin* / metabolism Sirtuin 1* / genetics Sirtuin 1* / metabolism |
| IF | 11.864 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01492 |