Hu Hai-Ting, Zhang Zhen-Yu, Luo Zi -Xin, Ti Hui-Bo, Wu Jun-Jie, Nie Hao, Yuan Zheng-Dong, Wu Xian, Zhang Ke-Yue, Shi Shu-Wen, Qian Yi-Qing, Wang Xin-Chen, Wu Jing-Jing, Li Xia, Yuan Feng-Lai
Institute of Integrated Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, Jiangsu, 214041, China.
Cell Death Discov. 2025 Jul 21;11(1):335. doi: 10.1038/s41420-025-02633-3.
The adult skeleton preserves its structural and functional integrity through continuous bone remodeling, a process tightly regulated by osteoblasts, osteoclasts, and osteocytes. Disruptions to this balance contribute to skeletal pathologies like osteoporosis and periodontitis, underscoring the need to understand the mechanisms governing bone homeostasis. Regulated cell death (RCD) plays a key role in bone remodeling by modulating the activity of osteoblasts and osteoclasts. Recent advances have revealed novel RCD modalities: ferroptosis, cuproptosis, disulfidptosis, and PANoptosis, each with unique molecular mechanisms and pathophysiological implications in bone disorders. So we want to elucidate the molecular mechanisms, signaling cascades, and roles of these four novel RCD modalities in bone remodeling and skeletal homeostasis. We explore their potential involvement in bone-related pathologies, emphasizing the crucial roles of osteoblasts, osteoclasts, and osteocytes in maintaining skeletal integrity. By synthesizing emerging evidence, we aim to identify therapeutic targets and propose innovative strategies for managing skeletal disorders, advancing research in bone health and providing novel insights for clinical translation. Emerging regulated cell death mechanisms in bone remodeling.
成人骨骼通过持续的骨重塑来维持其结构和功能的完整性,这一过程受到成骨细胞、破骨细胞和骨细胞的严格调控。这种平衡的破坏会导致骨质疏松症和牙周炎等骨骼疾病,凸显了了解骨稳态调控机制的必要性。调节性细胞死亡(RCD)通过调节成骨细胞和破骨细胞的活性在骨重塑中发挥关键作用。最近的进展揭示了新的RCD模式:铁死亡、铜死亡、二硫死亡和PANoptosis,每种模式在骨骼疾病中都有独特的分子机制和病理生理意义。因此,我们希望阐明这四种新的RCD模式在骨重塑和骨骼稳态中的分子机制、信号级联和作用。我们探讨它们在骨相关疾病中的潜在参与,强调成骨细胞、破骨细胞和骨细胞在维持骨骼完整性中的关键作用。通过综合新出现的证据,我们旨在确定治疗靶点,并提出管理骨骼疾病的创新策略,推动骨骼健康研究,并为临床转化提供新的见解。骨重塑中新兴的调节性细胞死亡机制。
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