Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes

Sheng-Long Ding; Zhi-Ying Pang; Xue-Mei Chen; Zheng Li; Xin-Xin Liu; Qi-Lin Zhai; Jun-Ming Huang; Zhi-Yong Ruan

doi:10.1186/s12950-020-00242-8

Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes

J Inflamm (Lond). 2020 Mar 24:17:13. doi: 10.1186/s12950-020-00242-8. eCollection 2020.

Authors

Sheng-Long Ding^#¹, Zhi-Ying Pang^#², Xue-Mei Chen^#³, Zheng Li², Xin-Xin Liu², Qi-Lin Zhai¹, Jun-Ming Huang², Zhi-Yong Ruan¹

Affiliations

¹ 1Department of Orthopaedic Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, 1158 Gong Yuan Dong Road, Qingpu District, Shanghai, 201700 China.
² 2Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032 China.
³ 3Department of Anesthesiology, Shanghai JiaoTong University Affiliated Shanghai Sixth People's Hospital, Shanghai, 200233 China.

^# Contributed equally.

Abstract

Background: Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1β (IL-1β)-induced chondrocytes.

Results: No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1β stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage. Mechanistically, IL-1β significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1β-induced injury by activating the mitogen-activated kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways.

Conclusion: Our results provide the evidence that UA could attenuate IL-1β-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.

Keywords: Inflammation; MAPK; NF-κB; Osteoarthritis; Urolithin a.