As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria‐targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH)₂, are assembled onto the sulfonated PEEK surface (Zn&Sr‐SPEEK). The results indicate the synergistic liberation of Zn²⁺ and Sr²⁺ from coating massacres pathogenic bacteria and dramatically facilitates cyto‐activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr‐SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia‐induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin‐related protein 1 (Drp1) gene down‐regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn²⁺ and Sr²⁺ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability.

Oxygen deficiency is associated with various oral diseases, including chronic periodontitis, age-related alveolar bone loss, and mechanical stress-linked cell injury from orthodontic appliances. Nevertheless, our understanding of the impact of hypoxia on periodontal tissues and its biochemical mechanism is still rudimentary. The purpose of this research was to elucidate the effects of hypoxia on the apoptosis of human periodontal ligament stem cells (PDLSCs) in vitro and the underlying mechanism. Herein, we showed that cobalt chloride (CoCl₂) triggered cell dysfunction in human PDLSCs in a concentration-dependent manner and resulted in cell apoptosis and oxidative stress overproduction and accumulation in PDLSCs. In addition, CoCl₂ promoted mitochondrial fission in PDLSCs. Importantly, CoCl₂ increased the expression of dynamin-related protein 1 (Drp1), the major regulator in mitochondrial fission, in PDLSCs. Mitochondrial division inhibitor-1, pharmacological inhibition of Drp1, not only inhibited mitochondrial fission but also protected against CoCl₂-induced PDLSC dysfunction, as shown by increased mitochondrial membrane potential, increased ATP level, reduced reactive oxygen species (ROS) level, and decreased apoptosis. Furthermore, N-acety-l-cysteine, a pharmacological inhibitor of ROS, also abolished CoCl₂-induced expression of Drp1 and protected against CoCl₂-induced PDLSC dysfunction, as shown by restored mitochondrial membrane potential, ATP level, inhibited mitochondrial fission, and decreased apoptosis. Collectively, our data provide new insights into the role of the ROS-Drp1-dependent mitochondrial pathway in CoCl₂-induced apoptosis in PDLSCs, indicating that ROS and Drp1 are promising therapeutic targets for the treatment of CoCl₂-induced PDLSC dysfunction.

Diabetes mellitus is a well‐recognized risk factor for periodontitis. The goal of the present study was to elucidate whether oxidative stress and nuclear factor erythroid 2‐related factor 2 (Nrf2) participate in the aggravation of periodontitis by diabetes. For this purpose, we assigned Wistar rats to control, periodontitis, diabetes, and diabetic periodontitis groups. Two weeks after induction of diabetes by streptozotocin, periodontitis was induced by ligation. Two weeks later, periodontal tissues and blood were harvested and analyzed by stereomicroscopy, immunohistochemistry, and real‐time polymerase chain reaction. We found that ligation induced more severe bone loss and periodontal cell apoptosis in diabetic rats than in normal rats (p < 0.05). Compared with the control group, periodontitis significantly enhanced local oxidative damage (elevated expression of 3‐nitrotyrosine, 4‐hydroxy‐2‐nonenal, and 8‐hydroxy‐deoxyguanosine), whereas diabetes significantly increased systemic oxidative damage and suppressed antioxidant capacity (increased malondialdehyde expression and decreased superoxide dismutase activity) (p < 0.05). Simultaneous periodontitis and diabetes synergistically aggravated both local and systemic oxidative damage (p < 0.05); this finding was strongly correlated with the more severe periodontal destruction in diabetic periodontitis. Furthermore, gene and protein expression of Nrf2 was significantly downregulated in diabetic periodontitis (p < 0.05). Multiple regression analysis indicated that the reduced Nrf2 expression was strongly correlated with the aggravated periodontal destruction and oxidative damage in diabetic periodontitis. We conclude that enhanced local and systemic oxidative damage and Nrf2 downregulation contribute to the development and progression of diabetic periodontitis.

The M2 isoform of pyruvate kinase (PKM2) is one isoform of pyruvate kinase (PK). PKM2 is expressed at high levels during embryonic development and tumor progression and is subject to complex allosteric regulation. PKM2 is a special glycolytic enzyme that regulates the final step of glycolysis; the role of PKM2 in the metabolism, survival, and apoptosis of cancer cells has received increasing attention. Mitochondria are directly or indirectly involved in the regulation of energy metabolism, susceptibility to oxidative stress, and cell death; however, the role of PKM2 in mitochondrial functions remains unclear. Herein, we review the related mechanisms of the role of PKM2 in the regulation of mitochondrial functions from the aspects of metabolism, reactive oxygen species (ROS), dynamic, and apoptosis, which can be highlighted as a target for the clinical management of cardiovascular and metabolic diseases.