You Yu, Huo Konglin, He Liang, Wang Tongyue, Zhao Lei, Li Rong, Cheng Xiaoqing, Ma Xuebin, Yue Zhiying, Siwko Stefan, Wang Ning, Liao Lujian, Liu Mingyao, Luo Jian
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, PR China.
Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, PR China.
Bone Res. 2025 Jan 21;13(1):13. doi: 10.1038/s41413-024-00389-7.
Reproductive hormones associated with the hypothalamic-pituitary-gonadal (HPG) axis are closely linked to bone homeostasis. In this study, we demonstrate that Gonadotropin inhibitory hormone (GnIH, one of the key reproductive hormones upstream of the HPG axis) plays an indispensable role in regulating bone homeostasis and maintaining bone mass. We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density (BMD) in mice primarily by enhancement of osteoclast activation in vivo and in vitro. Mechanistically, GnIH/Gpr147 inhibits osteoclastogenesis by the PI3K/AKT, MAPK, NF-κB and Nfatc1 signaling pathways. Furthermore, GnIH treatment was able to alleviate bone loss in aging, ovariectomy (OVX) or LPS-induced mice. Moreover, the therapy using green light promotes the release of GnIH and rescues OVX-induced bone loss. In humans, serum GnIH increases and bone resorption markers decrease after green light exposure. Therefore, our study elucidates that GnIH plays an important role in maintaining bone homeostasis via modulating osteoclast differentiation and demonstrates the potential of GnIH therapy or green light therapy in preventing osteoporosis.
与下丘脑-垂体-性腺（HPG）轴相关的生殖激素与骨稳态密切相关。在本研究中，我们证明促性腺激素抑制激素（GnIH，HPG轴上游的关键生殖激素之一）在调节骨稳态和维持骨量方面发挥着不可或缺的作用。我们发现，GnIH或其受体Gpr147的缺乏主要通过体内外增强破骨细胞活化导致小鼠骨矿物质密度（BMD）显著降低。机制上，GnIH/Gpr147通过PI3K/AKT、MAPK、NF-κB和Nfatc1信号通路抑制破骨细胞生成。此外，GnIH治疗能够减轻衰老、卵巢切除（OVX）或脂多糖诱导的小鼠的骨质流失。而且，绿光疗法促进GnIH释放并挽救OVX诱导的骨质流失。在人类中，绿光照射后血清GnIH增加而骨吸收标志物减少。因此，我们的研究阐明GnIH通过调节破骨细胞分化在维持骨稳态中发挥重要作用，并证明GnIH疗法或绿光疗法在预防骨质疏松症方面的潜力。
