ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Purinergic signaling in osteoarthritis: Mechanistic insights into pathogenesis and therapeutic targeting.Genes & diseases · 2026Review
- Mechanisms and therapeutic potential of AMPK signaling pathway in the regulation of lipid metabolism.Molecular biology reports · 2026Review
- Differential miRNA profiles in fluoride-exposed rBMSCs-EVs and the influence of miR-320-3p transfer on osteogenic differentiation.Stem cells translational medicine · 2026Article
- Molecular mechanisms of SIRT1 in regulating ageing and related intervention strategies.Molecular biology reports · 2026Review
- Dysregulation of the glycolysis-mitochondrial metabolism axis in osteoarthritis: mechanisms and therapeutic implications.Journal of orthopaedic translation · 2026Review
- Patellar luxation causes abnormal mechanical loading and joint destruction in the femoral-tibial joint.Bone & joint research · 2026Article
- Chinese Massage (Tuina) Attenuates Knee Osteoarthritis by Modulating Autophagy-Related Cytokines: A Multidisciplinary Methodological Investigation.Journal of inflammation research · 2025Article
- Modulating Autophagy in Osteoarthritis: Exploring Emerging Therapeutic Drug Targets.International journal of molecular sciences · 2024Review
- PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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14 authors.
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Abstract
The molecular mechanism underlying abnormal osteoclastogenesis triggering subchondral bone remodeling in osteoarthritis (OA) is still unclear. Here, single-cell and bulk transcriptomics sequencing analyses are performed on GEO datasets to identify key molecules and validate them using knee joint tissues from OA patients and rat OA models. It is found that the catalytic subunit of protein phosphatase 2A (PP2Ac) is highly expressed during osteoclastogenesis in the early stage of OA and is correlated with autophagy. Knockdown or inhibition of PP2Ac weakened autophagy during osteoclastogenesis. Furthermore, the ULK1 expression of the downstream genes is significantly increased when PP2Ac is knocked down. PP2Ac-mediated autophagy is dependent on ULK1 phosphorylation activity during osteoclastogenesis, which is associated with enhanced dephosphorylation of ULK1 Ser637 residue regulating at the post-translational level. Additionally, mTORC1 inhibition facilitated the expression level of PP2Ac during osteoclastogenesis. In animal OA models, decreasing the expression of PP2Ac ameliorated early OA progression. The findings suggest that PP2Ac is also a promising therapeutic target in early OA.
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