Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9.
Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9.
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DOI：
10.1016/j.isci.2024.108857
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发表时间：
2024-02-16
期刊：
影响因子：
5.8
通讯作者：
Zou, Zhipeng
中科院分区：
文献类型：
--
作者：
Wang, Ting;Zhao, Chaoran;Zhang, Jiahuan;Li, Shengfa;Zhang, Youming;Gong, Yan;Zhou, Yingyue;Yan, Lei;Zhang, Sheng;Zhang, Zhongmin;Hu, Hongling;Liu, Anling;And, Xiaochun;Zou, Zhipeng
棕色脂肪组织（BAT）调节骨代谢的机制尚不清楚。在这里，我们揭示了BAT分泌S100 A8/A9，一种以前未鉴定的BAT脂肪因子（batokine），以损害骨形成。棕色脂肪细胞特异性敲除mTOR的上游激活因子Rheb（RhebBAD KO）导致BAT功能障碍以抑制成骨。RheB耗竭诱导NF-κB依赖性S100 A8/A9从棕色脂肪细胞分泌，但不诱导巨噬细胞分泌。在野生型小鼠中，BAT中与年龄相关的Rheb下调与S100 A8/A9分泌增强有关。RhebBAD KO小鼠的batokines或重组S100 A8/A9通过靶向其表面的toll样受体4抑制体外间充质干细胞的成骨细胞分化。相反，S100 A8/A9中和不仅挽救了RhebBAD KO小鼠中受抑制的骨生成，而且还减轻了野生型小鼠中与年龄相关的骨质疏松症。总的来说，我们的数据揭示了由Rheb-S100 A8/A9驱动的意想不到的BAT-骨串扰，揭示了S100 A8/A9作为治疗和潜在预防骨质疏松症的有希望的靶点。Rheb的丧失诱导BAT功能障碍和S100 A8/A9的内分泌BAT衍生的S100 A8/A9抑制骨形成，诱导骨质疏松症中和S100 A8/A9恢复BAT功能障碍受损的骨形成S100 A8/A9通过靶向其TLR 4直接抑制BMSC的骨生成生理学;分子生物学;细胞生物学
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. Loss of Rheb induces BAT malfunction and endocrine secretion of S100A8/A9 BAT-derived S100A8/A9 inhibits bone formation, inducing osteoporosis Neutralizing S100A8/A9 restores bone formation impaired by BAT malfunction S100A8/A9 directly inhibits osteogenesis of BMSCs by targeting their TLR4 Physiology; Molecular biology; Cell biology
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影响因子：
14.9
作者：
Imrichová H;Hulselmans G;Atak ZK;Potier D;Aerts S
通讯作者：
Aerts S
DOI：
10.1359/jbmr.090805
发表时间：
2010-02
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Ecklund K;Vajapeyam S;Feldman HA;Buzney CD;Mulkern RV;Kleinman PK;Rosen CJ;Gordon CM
通讯作者：
Gordon CM
影响因子：
29
作者：
Cereijo, Ruben;Gavalda-Navarro, Aleix;Villarroya, Francesc
通讯作者：
Villarroya, Francesc
DOI：
10.1007/978-1-4939-9195-2_18
发表时间：
2019-01-01
期刊：
NUCLEAR RECEPTORS: METHODS AND EXPERIMENTAL PROTOCOLS
影响因子：
--
作者：
Ampem, Grace;Roeszer, Tamas
通讯作者：
Roeszer, Tamas
影响因子：
9.8
作者：
Gallego-Escuredo, Jose M.;Karuna Lamarca, Maria;Giralt, Marta
通讯作者：
Giralt, Marta