Objective To summarize the role of chondrocytes mitochondrial biogenesis in the pathogenesis of osteoarthritis (OA), and analyze the applications in the treatment of OA. Methods A review of recent literature was conducted to summarize the changes in mitochondrial biogenesis in the course of OA, the role of major signaling molecules in OA chondrocytes, and the prospects for OA therapeutic applications. Results Recent studies reveales that mitochondria are significant energy metabolic centers in chondrocytes and its dysfunction has been considered as an essential mechanism in the pathogenesis of OA. Mitochondrial biogenesis is one of the key processes maintaining the normal quantity and function of mitochondria, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is the central regulator of this process. A regulatory network of mitochondrial biogenesis with PGC-1α as the center, adenosine monophosphate-activated protein kinase, sirtuin1/3, and cyclic adenosine monophosphate response element-binding protein as the main upstream regulatory molecules, and nuclear respiratory factor 1, estrogen-related receptor α, and nuclear respiratory factor 2 as the main downstream regulatory molecules has been reported. However, the role of mitochondrial biogenesis in OA chondrocytes still needs further validation and in-depth exploration. It has been demonstrated that substances such as puerarin and omentin-1 can retard the development of OA by activating the damaged mitochondrial biogenesis in OA chondrocytes, which proves the potential to be used in the treatment OA. ConclusionMitochondrial biogenesis in chondrocytes plays an important role in the pathogenesis of OA, and further exploring the related mechanisms is of great clinical significance.
Objective To review the research progress on lactylation modification in the pathogenesis of osteoarthritis (OA). Methods Relevant studies published in recent years on lactate metabolism and lactylation modification in OA were retrieved and analyzed, summarizing the molecular mechanisms of lactylation and its regulatory roles in different cells and pathological processes. Results Lactate, as the major metabolic product of glycolysis, not only participates in energy metabolism but also plays a crucial role in OA progression through lactylation modification. Lactate-driven histone and non-histone lactylation regulate gene transcription and cellular functions, contributing to chondrocyte metabolic reprogramming, extracellular matrix (ECM) synthesis and degradation, cell proliferation and apoptosis, as well as ferroptosis. In fibroblast-like synoviocytes, lactylation modification promotes cellular senescence and the release of inflammatory factors; in immune cells, lactylation regulates inflammatory responses by influencing macrophage polarization and intercellular communication. Overall, lactylation modification exhibits a dual effect in OA: it aggravates ECM degradation and inflammation on the one hand, but under specific microenvironments, it also promotes repair and regeneration. However, the site-specificity, cell-type heterogeneity, and cross-talk of lactylation with other epigenetic modifications remain to be further clarified. Conclusion Lactylation modification provides a novel perspective for understanding the metabolic and epigenetic mechanisms of OA and may serve as a potential biomarker and therapeutic target. Future studies combining multi-omics approaches to map the global lactylation landscape, together with small-molecule inhibitors, epigenetic editing tools, and regenerative medicine strategies, may enable precise regulation of lactylation, offering new strategies to delay or even reverse OA progression.
