Abstract | BACKGROUND: METHODS: NPCs were treated with IL-1β to mimic apoptosis, followed by the addition of TAK-715. It was determined that apoptosis, inflammatory mediators (COX-2), inflammatory cytokines ( HMGB1), and ECM components ( collagen II, MMP9, ADAMTS5, and MMP3) existed in NPCs. In addition, the p38MAPK signaling pathways were examined. The role of TAK-715 in vivo was determined by acupuncture-induced intervertebral disc degeneration. Following an intradiscal injection of TAK-715, MRI and a histopathological analysis were conducted to assess the degree of degeneration. RESULTS: IL-1β-induced apoptosis was alleviated by TAK-715 in vitro, and antiapoptotic proteins were upregulated. Furthermore, TAK-715 blocked IL-1β-induced inflammatory mediator production (COX-2) and inflammatory cytokine production ( HMGB1) and degraded the ECM ( collagen II, MMP9, ADAMTS5, and MMP3). By inhibiting the phosphorylation of p38, TAK-715 exerted its effects. In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations. CONCLUSION:
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Authors | Kun Wang, Dengbo Yao, Yuxi Li, Ming Li, Weike Zeng, Zhuangyao Liao, Engming Chen, Shixin Lu, Kaihui Su, Zhen Che, Yuwei Liang, Peng Wang, Lin Huang |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 25
Issue 1
Pg. 45
(03 21 2023)
ISSN: 1478-6362 [Electronic] England |
PMID | 36945021
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2023. The Author(s). |
Chemical References |
- Cyclooxygenase 2
- HMGB1 Protein
- Matrix Metalloproteinase 3
- Matrix Metalloproteinase 9
- N-(4-(2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl)-2-pyridyl)benzamide
- Interleukin-1beta
- Benzamides
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Topics |
- Animals
- Rats
- Apoptosis
- Cyclooxygenase 2
(metabolism)
- HMGB1 Protein
(metabolism)
- Intervertebral Disc
(pathology)
- Intervertebral Disc Degeneration
(drug therapy)
- Matrix Metalloproteinase 3
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Nucleus Pulposus
(cytology, pathology)
- Interleukin-1beta
(pharmacology)
- Extracellular Matrix
(pathology)
- Benzamides
(pharmacology)
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