Tongling Huang, Zhaocheng Lu, Zihui Wang, Lixin Cheng, Lu Gao, Jun Gao, Ning Zhang, Chang-An Geng, Xiaoli Zhao, Huaiyu Wang, Chi-Wai Wong, Kelvin W K Yeung, Haobo Pan, William Weijia Lu, Min Guan
Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter...
May 4, 2024: Nature Communications