The Role of Gene–Environment Interactions in Metabolic Dysregulation in Osteochondral Disease Pathogenesis

Dear Colleagues,

This Special Issue focuses on elucidating the tripartite interplay between genetic susceptibility, environmental exposures, and resultant metabolic dysregulation in driving the pathogenesis of osteochondral diseases (e.g., osteoarthritis, osteochondritis dissecans, Kashin–Beck disease, spinal disk degeneration). We prioritize research uncovering how gene–environment interactions affect cellular metabolism (e.g., nutrient sensing, energy homeostasis, redox balance, lipid/glucose flux) within joint tissues (articular cartilage, subchondral bone, growth plate), ultimately leading to matrix degradation, aberrant remodeling, and tissue failure.

We invite high-quality original research and reviews addressing, but not limited to, the following: 1. Molecular Mechanisms: epigenetic regulation (DNA methylation, histone modifications, ncRNAs) induced by dietary factors, toxins, mechanical stress, or inflammation that alters metabolic gene expression. 2. Metabolic Pathways: dysregulation in chondrocyte/bone cell metabolism (mitochondrial dysfunction, glycolysis, autophagy, mTOR signaling) triggered by gene–environment interactions. 3. Environmental Triggers: impact of obesity-associated metabolites, micronutrient deficiencies, endocrine disruptors, biomechanical overload, or gut microbiome-derived metabolites. 4. Genetic Vulnerabilities: polymorphisms/metabolic quantitative trait loci (mQTLs) in nutrient-sensing (e.g., AMPK, SIRT1), anabolic/catabolic (e.g., HIFs, SOX9, MMPs), or stress-response pathways that modulate environmental sensitivity. 5. Interventional Strategies: dietary, pharmacological, or biomechanical approaches targeting gene–environment interactions-mediated metabolic pathology.

Osteochondral diseases impose a massive global burden, yet their pathogenesis remains incompletely understood, hindering disease-modifying therapy development. We seek contributions that advance mechanistic insights and translational applications, ultimately paving the way for precision medicine in osteochondral disorders.

Dr. Xi Wang
Dr. Lei Yang
Guest Editors

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