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Cited by 24Osteoarthritis Treatment and MechanismsNatural Compounds in Disease TreatmentBone Metabolism and Diseases

Pseudolaric acid B ameliorates synovial inflammation and vessel formation by stabilizing PPARγ to inhibit NF‐κB signalling pathway

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Lu, Jiansen, Guan, Hong, Wu, Dan, Hu, Zhiqiang, Zhang, Hongbo, Jiang, Huaji, Yu, Jingyao, Zeng, Ke +5 more·2021·Journal of Cellular and Molecular Medicine
DOI 10.1111/jcmm.16670PMC PMC8278075
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Abstract

Synovial macrophage polarization and inflammation are essential for osteoarthritis (OA) development, yet the molecular mechanisms and regulation responsible for the pathogenesis are still poorly understood. Here, we report that pseudolaric acid B (PAB) attenuated articular cartilage degeneration and synovitis during OA. PAB, a diterpene acid, specifically inhibited NF‐κB signalling and reduced the production of pro‐inflammatory cytokines, which further decreased M1 polarization and vessel formation. We further provide in vivo and in vitro evidences that PAB suppressed NF‐κB signalling by stabilizing PPARγ. Using PPARγ antagonist could abolish anti‐inflammatory effect of PAB and rescue the activation of NF‐κB signalling during OA. Our findings identify a previously unrecognized role of PAB in the regulation of OA and provide mechanisms by which PAB regulates NF‐κB signalling through PPARγ, which further suggest targeting synovial inflammation or inhibiting vessel formation at early stage could be an effective preventive strategy for OA.

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Cited by

Sorted by citations

Authors
Lu, J., Guan, H., Wu, D., Hu, Z., Zhang, H., Jiang, H., Yu, J., Zeng, K., Li, H., Zhang, H., Pan, C., Cai, D., & Yu, X.
Affiliations
  • Third Affiliated Hospital of Southern Medical University (CN)
  • Southern Medical University (CN)
  • Gannan Medical University (CN)
Corresponding author
  • Pan, Chenglong
  • Cai, Daozhang
  • Yu, Xiao
ORCID
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2021-06-11
Volume
25
Issue
14
Pages
6664-6678
ISSN
  • 1582-1838 (ISSN-L)
  • 1582-4934
DOI
10.1111/jcmm.16670
PMC
PMC8278075
OpenAlex
W3169455671
Cited by
24
References
1
Citations by year
2026: 3 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 2 · 2021: 1
FWCI
3.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81902229, 81772406, 81974341, 81801579)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
pseudolaric acid B, osteoarthritis, synovitis, M1 macrophages, angiogenesis, NF-κB signaling, inflammatory cytokines, articular cartilage degeneration, diterpene acids, anti-inflammatory therapy
MeSH terms
RAW 264.7 Cells, Animals, Blood Vessels, Cartilage, Articular, Disease Models, Animal, Diterpenes, Humans, Inflammation, Osteoarthritis, Synovitis, Signal Transduction, NF-kappa B, Chondrocytes, PPAR gamma, Mice, Transcription Factor RelA

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