Excess glucocorticoids inhibit murine bone turnover via modulating the immunometabolism of the skeletal microenvironment
Elevated bone resorption and diminished bone formation have been recognized as the primary features of glucocorticoid-associated skeletal disorders. However, the direct effects of excess glucocorticoids on bone turnover remains unclear. Here, we explored the outcomes of exogenous glucocorticoid treatment on bone loss and delayed fracture healing in mice and found that reduced bone turnover was a dominant feature, resulting in a net loss of bone mass. The primary effect of glucocorticoids on osteogenic differentiation was not inhibitory; instead, they cooperated with macrophages to facilitate osteogenesis. Impaired local nutrient status, notably, obstructed fatty acid transportation, was a key factor contributing to glucocorticoid-induced impairment of bone turnover in vivo. Furthermore, fatty acid oxidation in macrophages fueled the ability of glucocorticoid-liganded receptors to enter the nucleus and then promoted the expression of Bmp2, a key cytokine that facilitates osteogenesis. Metabolic reprogramming by localized fatty acid delivery partly rescued glucocorticoid-induced pathology by restoring a healthier immune-metabolic milieu. These data provide insights into the multifactorial metabolic mechanisms by which glucocorticoids generate skeletal disorders, thus suggesting possible therapeutic avenues.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
The Journal of clinical investigation - (2024) vom: 21. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Xu [VerfasserIn] |
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| Links: |
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| Themen: |
Bone biology |
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| Anmerkungen: |
Date Revised 21.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1172/JCI166795 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Excess glucocorticoids inhibit murine bone turnover via modulating the immunometabolism of the skeletal microenvironment |
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| 520 | |a Elevated bone resorption and diminished bone formation have been recognized as the primary features of glucocorticoid-associated skeletal disorders. However, the direct effects of excess glucocorticoids on bone turnover remains unclear. Here, we explored the outcomes of exogenous glucocorticoid treatment on bone loss and delayed fracture healing in mice and found that reduced bone turnover was a dominant feature, resulting in a net loss of bone mass. The primary effect of glucocorticoids on osteogenic differentiation was not inhibitory; instead, they cooperated with macrophages to facilitate osteogenesis. Impaired local nutrient status, notably, obstructed fatty acid transportation, was a key factor contributing to glucocorticoid-induced impairment of bone turnover in vivo. Furthermore, fatty acid oxidation in macrophages fueled the ability of glucocorticoid-liganded receptors to enter the nucleus and then promoted the expression of Bmp2, a key cytokine that facilitates osteogenesis. Metabolic reprogramming by localized fatty acid delivery partly rescued glucocorticoid-induced pathology by restoring a healthier immune-metabolic milieu. These data provide insights into the multifactorial metabolic mechanisms by which glucocorticoids generate skeletal disorders, thus suggesting possible therapeutic avenues | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bone biology | |
| 650 | 4 | |a Bone disease | |
| 650 | 4 | |a Fatty acid oxidation | |
| 650 | 4 | |a Osteoporosis | |
| 700 | 1 | |a Liang, Tongzhou |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Bingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Shiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Jiaxin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shunxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Lizhen |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Lian, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ye |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Wenxue |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinluan |e verfasserin |4 aut | |
| 700 | 1 | |a Chow, Dick Ho Kiu |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jiankun |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Ling |e verfasserin |4 aut | |
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