Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9
© 2024 The Authors..
The mechanism by which brown adipose tissue (BAT) regulates bone metabolism is unclear. Here, we reveal that BAT secretes S100A8/A9, a previously unidentified BAT adipokine (batokine), to impair bone formation. Brown adipocytes-specific knockout of Rheb (RhebBAD KO), the upstream activator of mTOR, causes BAT malfunction to inhibit osteogenesis. Rheb depletion induces NF-κB dependent S100A8/A9 secretion from brown adipocytes, but not from macrophages. In wild-type mice, age-related Rheb downregulation in BAT is associated with enhanced S100A8/A9 secretion. Either batokines from RhebBAD KO mice, or recombinant S100A8/A9, inhibits osteoblast differentiation of mesenchymal stem cells in vitro by targeting toll-like receptor 4 on their surfaces. Conversely, S100A8/A9 neutralization not only rescues the osteogenesis repressed in the RhebBAD KO mice, but also alleviates age-related osteoporosis in wild-type mice. Collectively, our data revealed an unexpected BAT-bone crosstalk driven by Rheb-S100A8/A9, uncovering S100A8/A9 as a promising target for the treatment, and potentially, prevention of osteoporosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
iScience - 27(2024), 2 vom: 16. Feb., Seite 108857 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Ting [VerfasserIn] |
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| Anmerkungen: |
Date Revised 03.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2024.108857 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367930714 |
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| 520 | |a The mechanism by which brown adipose tissue (BAT) regulates bone metabolism is unclear. Here, we reveal that BAT secretes S100A8/A9, a previously unidentified BAT adipokine (batokine), to impair bone formation. Brown adipocytes-specific knockout of Rheb (RhebBAD KO), the upstream activator of mTOR, causes BAT malfunction to inhibit osteogenesis. Rheb depletion induces NF-κB dependent S100A8/A9 secretion from brown adipocytes, but not from macrophages. In wild-type mice, age-related Rheb downregulation in BAT is associated with enhanced S100A8/A9 secretion. Either batokines from RhebBAD KO mice, or recombinant S100A8/A9, inhibits osteoblast differentiation of mesenchymal stem cells in vitro by targeting toll-like receptor 4 on their surfaces. Conversely, S100A8/A9 neutralization not only rescues the osteogenesis repressed in the RhebBAD KO mice, but also alleviates age-related osteoporosis in wild-type mice. Collectively, our data revealed an unexpected BAT-bone crosstalk driven by Rheb-S100A8/A9, uncovering S100A8/A9 as a promising target for the treatment, and potentially, prevention of osteoporosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cell biology | |
| 650 | 4 | |a Molecular biology | |
| 650 | 4 | |a Physiology | |
| 700 | 1 | |a Zhao, Chaoran |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jiahuan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shengfa |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Youming |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yingyue |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhongmin |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Hongling |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Anling |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Xiaochun |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Zhipeng |e verfasserin |4 aut | |
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