Mechanical overloading leads to chondrocyte degeneration and senescence via Zmpste24-mediated nuclear membrane instability

Kong, Keyu; Jin, Minghao; Zhao, Chen; Qiao, Hua; Chen, Xuzhuo; Li, Baixing; Rong, Kewei; Zhang, Pu; Shan, Yu; Xu, Zhengquan; Chang, Yongyun; Li, Huiwu; Zhai, Zanjing

doi:10.1016/j.isci.2023.108119

iScience

2023

DOI: 10.1016/j.isci.2023.108119

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Mechanical overloading leads to chondrocyte degeneration and senescence via Zmpste24-mediated nuclear membrane instability

Keyu Kong,

Minghao Jin,

Chen Zhao

et al.

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2024

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Cited by 2 publications

References 49 publications

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A Ubiquitin‐Competitive Strategy Based on the Element Microenvironment to Treat Osteoarthritis

Kong,

Yang,

Chang

et al. 2024

Adv Funct Materials

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Recent research on ferroptosis and cuproptosis has underscored the crucial role of trace element regulation in osteoarthritis (OA) treatment. However, research systematically addressing the alterations in nutrient elements in OA cartilage is lacking. This study is initiated using clinical specimens to quantify metal element concentrations in both damaged and intact cartilage to identify deficient trace elements within the inflammatory and senescent microenvironments of OA. Based on the preliminary findings of selenium (Se) and gallium (Ga) deficiencies in OA cartilage, tailored nanoparticles based on Se and Ga are designed and validated for their antioxidant ability. GaSex nanoparticles demonstrated significant efficacy in mitigating chondrocyte degeneration and extracellular matrix degradation induced by inflammatory factors and in alleviating cartilage abrasion, hyperalgesia, and abnormal gait in a destabilization of the medial meniscus (DMM) mouse model. Mechanistically, GaSex nanoparticles activated the Nrf2 pathway and competitively inhibited the ubiquitin‐mediated degradation of Gpx4, thus inhibiting ferroptosis. This study systematically designed GaSex nanoparticles based on the imbalance of trace elements within the OA knee joint microenvironment and demonstrated robust antioxidant capabilities and remarkable competitive properties for ubiquitin, thereby providing a novel therapeutic solution for OA treatment.

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A Ubiquitin‐Competitive Strategy Based on the Element Microenvironment to Treat Osteoarthritis

Kong,

Yang,

Chang

et al. 2024

Adv Funct Materials

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Lipid remodeling in context of cellular senescence

Tighanimine

2024

Biochimie

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Mechanical overloading leads to chondrocyte degeneration and senescence via Zmpste24-mediated nuclear membrane instability

Cited by 2 publications

References 49 publications

A Ubiquitin‐Competitive Strategy Based on the Element Microenvironment to Treat Osteoarthritis

A Ubiquitin‐Competitive Strategy Based on the Element Microenvironment to Treat Osteoarthritis

Lipid remodeling in context of cellular senescence

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