Emerging regulated cell death mechanisms in bone remodeling: decoding ferroptosis, cuproptosis, disulfidptosis, and PANoptosis as therapeutic targets for skeletal disorders.

Abstract

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.