Department of Orthopaedic Surgery, Orthopaedic Research Institute, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.
Published: December 2024
AI Article Synopsis
Article Abstract
Chondrocyte senescence is a key driver of osteoarthritis (OA). Mitochondrial dysfunction and oxidative stress can induce chondrocyte senescence. However, the specific mechanisms by which senescence contributes to OA progression are not fully understood. Here, it is attested that Dipeptidyl peptidase 4 (DPP4) is significantly upregulated in osteoarthritic chondrocytes in both humans and mice. DPP4 promotes oxidative stress and cellular senescence in chondrocytes through excessive mitochondrial fission in an enzyme-independent manner. Intra-articular injection of adeno-associated virus 2 to upregulate DPP4 in chondrocytes promotes post-traumatic and aging-induced OA in mice in an enzyme-independent manner. Mechanistically, DPP4 competitively binds to Myosin heavy chain 9 (MYH9), interfering with its E3 ubiquitin ligase Carboxyl terminus of Hsc70-interacting protein (CHIP), and thereby upregulates MYH9 expression. Finally, a small molecule, 4,5-Dicaffeoylquinic acid is identified, which disrupts the interaction between DPP4 and MYH9, thereby ameliorating post-traumatic and aging-induced OA in mice caused by DPP4 upregulation. The study indicates that the non-enzymatic activity of DPP4 is a promising target for OA treatment.
Department of Orthopaedic Surgery, Orthopaedic Research Institute, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.
Chondrocyte senescence is a key driver of osteoarthritis (OA). Mitochondrial dysfunction and oxidative stress can induce chondrocyte senescence. However, the specific mechanisms by which senescence contributes to OA progression are not fully understood.
Background/aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking.
Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC.
Division of Environmental Medicine, Department of Medicine Grossman School of Medicine, New York University, 341 East 25th Street, New York, NY, 10010, USA.
While EZH2 enzymatic activity is well-known, emerging evidence suggests that EZH2 can exert functions in a methyltransferase-independent manner. In this study, we have uncovered a novel mechanism by which EZH2 positively regulates the expression of SKP2, a critical protein involved in cell cycle progression. We demonstrate that depletion of EZH2 significantly reduces SKP2 protein levels in several cell types, while treatment with EPZ-6438, an EZH2 enzymatic inhibitor, has no effect on SKP2 protein levels.
Gram-positive bacteria use SigI/RsgI-family sigma factor/anti-sigma factor pairs to sense and respond to cell wall defects and plant polysaccharides. In this signal transduction pathway involves regulated intramembrane proteolysis (RIP) of the membrane-anchored anti-sigma factor RsgI. However, unlike most RIP signaling pathways, site-1 cleavage of RsgI on the extracytoplasmic side of the membrane is constitutive and the cleavage products remain stably associated, preventing intramembrane proteolysis.
State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai, P.R. China.
Unlabelled: The KEAP1-NRF2 axis is the principal regulator of cellular responses to oxidative and electrophilic stressors. NRF2 hyperactivation is frequently observed in many types of cancer and promotes cancer initiation, progression, metastasis, and resistance to various therapies. Here, we determined that dipeptidyl peptidase 9 (DPP9) is a regulator of the KEAP1-NRF2 pathway in clear cell renal cell carcinoma (ccRCC).
