Research Paper Volume 12, Issue 2 pp 1760—1777

Nesfatin-1 suppresses interleukin-1β-induced inflammation, apoptosis, and cartilage matrix destruction in chondrocytes and ameliorates osteoarthritis in rats

Lifeng Jiang 1, *, , Kai Xu 1, *, , Jin Li 3, , Xindie Zhou 2, , Langhai Xu 1, , Zhipeng Wu 1, , Chiyuan Ma 1, , Jisheng Ran 1, , Pengfei Hu 1, , Jiapeng Bao 1, , Lidong Wu 1, , Yan Xiong 1, ,

  • 1 Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
  • 2 Department of Orthopedics, The Affiliated Changzhou People’s Hospital of Nanjing Medical University, Changzhou 213003, China
  • 3 Department of Orthopedics Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 31400, China
* Equal contribution and co-first authors

received: August 14, 2019 ; accepted: January 2, 2020 ; published: January 30, 2020 ;

https://doi.org/10.18632/aging.102711
How to Cite

Copyright © 2020 Jiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease, related to the overexpression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), inflammation, and chondrocyte apoptosis. Nesfatin-1 is an adipokine, which plays an important role in the development of OA, especially in obese people. In the present study, cartilage degradation and apoptosis observed in OA patients was evaluated. Furthermore, the anti-inflammatory and anti-apoptotic effects of nesfatin-1, and its underlying in vitro and in vivo mechanisms were investigated. The results showed that nesfatin-1 increased significantly the expression of collagen type II alpha 1 chain (Col2a1), and reduced the expression of MMPs, ADAMTS5, cyclooxygenase (COX)-2, caspase-3, nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), interleukin (IL)-6, and chondrocyte apoptosis rate, which may be induced by IL-1β in rat chondrocytes. Furthermore, nesfatin-1 treatment prevented cartilage degeneration in the rat OA model. It was found that nesfatin-1 suppressed the IL-1β-induced activation of NF-κB, the mitogen-activated protein kinase (MAPK), and the Bax/Bcl-2 signal pathway in chondrocytes. These results suggest that in vivo nesfatin-1 could play a protective role in the development of OA and can be potentially used for its treatment.

Abbreviations

OA: osteoarthritis; MMPs: matrix metalloproteinases; ADAMTS: a disintegrin and metalloproteinase with thrombospondin motifs; Col2a1: collagen type II alpha 1 chain; COX-2: cyclooxygenase-2; NO: nitric oxide; iNOS: inducible nitric oxide synthase; PGE2: prostaglandin E2; IL: interleukin; MAPK: mitogen-activated protein kinase; NSAIDs: nonsteroidal anti-inflammatory drugs; VSMCs: vascular smooth muscle cells; PBS: phosphate buffer saline; DMEM: Dulbecco's Modified Eagle Medium; FBS: fetal bovine serum; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; CCK-8: cell-counting kit-8 assay; H&E: hematoxylin and eosin stain; IHC: immunohistochemistry; HRP: horseradish peroxidase; SD: Sprague-Dawley; ELISA: enzyme-linked immunosorbent assay; PCR: polymerase chain reaction; BCA: bicinchoninic acid; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF: polyvinylidene fluoride; TBST: Tris-buffered saline with Tween; MM: medial meniscectomy; ANOVA: analysis of variance.