PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis
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.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis ; day:23 ; month:07 ; year:2024 ; extent:16
Advanced science ; (23.07.2024) (gesamt 16)
- Urheber
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Zhang, Haifeng
Ge, Gaoran
Zhang, Wei
Sun, Houyi
Liang, Xiaolong
Xia, Yu
Du, Jiacheng
Wu, Zerui
Bai, Jiaxiang
Yang, Huilin
Yang, Xing
Zhou, Jun
Xu, Yaozeng
Geng, Dechun
- DOI
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10.1002/advs.202404080
- URN
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urn:nbn:de:101:1-2407241410512.360295149470
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:45 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Zhang, Haifeng
- Ge, Gaoran
- Zhang, Wei
- Sun, Houyi
- Liang, Xiaolong
- Xia, Yu
- Du, Jiacheng
- Wu, Zerui
- Bai, Jiaxiang
- Yang, Huilin
- Yang, Xing
- Zhou, Jun
- Xu, Yaozeng
- Geng, Dechun
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