Mitochondrial quality control as a unifying regulatory platform in inflammatory bone diseases

Abstract

Inflammatory bone diseases, including periodontitis, osteoporosis, and osteoarthritis, are traditionally investigated as distinct pathological entities, despite sharing common features of chronic inflammation and impaired tissue regeneration. A unifying regulatory framework that mechanistically links these conditions, however, remains largely undefined. Here, we propose mitochondrial quality control (MQC) as a unifying regulatory platform that integrates inflammatory signaling, cellular metabolic fitness, and fate determination within bone and joint microenvironments. MQC comprises coordinated processes that maintain mitochondrial homeostasis, including mitochondrial dynamics, mitophagy, biogenesis, and emerging mechanisms such as mitochondrial-derived vesicles, mitocytosis, mitochondrial unfolded protein response, and mitochondrial transfer. Disruption of these pathways amplifies oxidative stress and inflammatory cascades, promoting cellular senescence and apoptosis, thereby exacerbating bone loss and cartilage degradation. This review highlights MQC dysfunction as a shared pathological axis across inflammatory bone diseases rather than a disease-specific consequence. Importantly, we frame MQC as a programmable therapeutic platform and propose a stratified intervention paradigm, in which stage-dependent modulation of mitochondrial quality, ranging from pharmacological regulation to nanotechnology-enabled mitochondrial repair and mitochondrial transfer, may enable precision treatment. This framework positions MQC at the interface of inflammation, metabolism, and regeneration, offering a multidisciplinary perspective for the development of next-generation therapies for inflammatory bone diseases.