Excess glucocorticoids inhibit murine bone turnover via modulating the immunometabolism of the skeletal microenvironment
Publication in refereed journal
香港中文大學研究人員
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摘要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 remain 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.
出版社接受日期15.03.2024
著者Xu Li, Tongzhou Liang, Bingyang Dai, Liang Chang, Yuan Zhang, Shiwen Hu, Jiaxin Guo, Shunxiang Xu, Lizhen Zheng, Hao Yao, Hong Lian, Yu Nie, Ye Li, Xuan He, Zhi Yao, Wenxue Tong, Xinluan Wang, Dick Ho Kiu Chow, Jiankun Xu, Ling Qin
期刊名稱Journal of Clinical Investigation
出版年份2024
月份5
日期15
卷號134
期次10
出版社American Society for Clinical Investigation
文章號碼134
國際標準期刊號0021-9738
電子國際標準期刊號1558-8238
語言美式英語
關鍵詞Bone biology, Bone disease, Fatty acid oxidation, Osteoporosis.
