1. Academic Validation
  2. Protectin DX attenuates IL-1β-induced inflammation via the AMPK/NF-κB pathway in chondrocytes and ameliorates osteoarthritis progression in a rat model

Protectin DX attenuates IL-1β-induced inflammation via the AMPK/NF-κB pathway in chondrocytes and ameliorates osteoarthritis progression in a rat model

  • Int Immunopharmacol. 2020 Jan;78:106043. doi: 10.1016/j.intimp.2019.106043.
Shang Piao 1 Wei Du 2 Yingliang Wei 1 Yue Yang 1 Xinyuan Feng 1 Lunhao Bai 3
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, ShengJing Hospital, China Medical University, Shenyang, PR China.
  • 2 Department of Anesthesiology, Liaoning Cancer Hospital and Institute, Shenyang, PR China.
  • 3 Department of Orthopedic Surgery, ShengJing Hospital, China Medical University, Shenyang, PR China. Electronic address: bailhsjh@163.com.
Abstract

Protectin DX (PDX) has been reported to have extensive anti-inflammatory effects. However, it is unknown whether PDX acts as an anti-inflammatory agent in the context of osteoarthritis (OA). This study aimed to evaluate the anti-inflammatory activity of PDX in vitro and in vivo in a model of OA. Primary rat chondrocytes were preincubated with PDX 1 h prior to IL-1β treatment for 24 h. We found that PDX was nontoxic, and pretreatment with PDX increased cell viability in IL-1β-induced chondrocytes. Preincubation with PDX also efficiently inhibited the degradation of type II collagen dose-dependently. Additionally, the expression of MMP-3, MMP-13, ADAMTS4, iNOS, COX-2, NO, and PGE2 decreased after IL-1β stimulation when cells were preincubated with PDX. Moreover, PDX inhibited the increase in phosphorylated NF-κB p65 and IκBα upon IL-1β stimulation, and the negative effects of IL-1β on chondrocytes were partially blocked by treatment with pyrrolidine dithiocarbamate (PDTC), a selective NF-κB Inhibitor. In addition, we found that PDX increased AMPK phosphorylation in IL-1β-mediated chondrocytes. The phosphorylation of AMPK could be inhibited by compound C, a classic AMPK Inhibitor. Compound C also remarkably reversed the decrease in p65 phosphorylation and MMP-13 expression caused by PDX. Furthermore, nuclear translocation of NF-κB was visible by immunofluorescence after PDX-induced AMPK activation. Additionally, we verified that PDX ameliorated cartilage degradation in monosodium iodoacetate (MIA)-induced OA rats through histological evaluation and ELISA of TNF-α in the serum and intra-articular lavage fluid. In conclusion, we have shown that PDX suppresses inflammation in chondrocytes in vitro and in vivo, likely through the AMPK/NF-κB signaling pathway. Our results suggest that PDX could be a useful novel therapeutic agent for OA treatment.

Keywords

AMP-activated protein kinase (AMPK); Chondrocyte; Nuclear factor-κB (NF-κB); Osteoarthritis (OA); Protectin DX (PDX).

Figures
Products