Research Paper Volume 12, Issue 13 pp 12799—12811
Tomatidine suppresses inflammation in primary articular chondrocytes and attenuates cartilage degradation in osteoarthritic rats
- 1 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
- 2 Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
Received: February 5, 2020 Accepted: March 31, 2020 Published: July 5, 2020https://doi.org/10.18632/aging.103222
How to Cite
Copyright © 2020 Chu 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.
In this study, we investigated whether the anti-inflammatory effects of tomatidine alleviate osteoarthritis (OA)-related pathology in primary articular chondrocytes and a rat OA model. STITCH database analysis identified 22 tomatidine-target genes that were enriched in 78 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Moreover,39 of the 105 OA-related KEGG pathways were related to tomatidine-target genes. The top two OA-related KEGG pathways with tomatidine-target genes were the MAPK and neutrophin signaling pathways. Pretreating primary chondrocytes with tomatidine suppressed interleukin-1β (IL-1β)-induced expression of iNOS, COX-2, MMP1, MMP3, MMP13, and ADAMTS-5. Tomatidine also suppressed IL-1β-induced degradation of collagen-II and aggrecan proteins by inhibiting NF-κB and MAPK signaling. In a rat OA model, histological and immunohistochemical analyses showed significantly less cartilage degeneration in thetibiofemoral joints of rats treated for 12 weeks with tomatidine after OA induction (experimental group) than in untreated OA group rats. However, micro-computed tomography (μ-CT) showed that tomatidine did not affect remodeling of the subchondral bone at the tibial plateau. These data shows that tomatidine suppresses IL-1β-induced inflammation in primary chondrocytes by inhibiting the NF-κB and MAPK signaling pathways, and protects against cartilage destruction in a rat OA model.