Journal Article

Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice

Cheng Yangyang, Gan Guosheng, Meng Biying, Tong Jiayue, Sun, Yin, Xu, Jinling, Guangda, Xiang, He Kaiyue, Shi Lingfeng, Xu, Xiaoli

2022

Overview

Osteoarthritis (OA) is characterized by chondrocyte apoptosis and increased degradation of type II collagen. Inflammation is one of the major risk factors involved in the pathophysiology of OA. Neuregulin 4 (Nrg4) plays a protective role in a variety of low-level inflammatory diseases, such as non-alcoholic fatty liver disease, inflammatory bowel disease, or type 2 diabetes mellitus. Here we found that (1) Nrg4 deficiency aggravated the destruction and inflammation of articular cartilage and the apoptosis of chondrocytes in vivo. (2) Nrg4 restoration reversed these changes in vivo. (3) Murine recombinant Nrg4 (rNrg4) suppressed inflammation and apoptosis of chondrocytes and decreased the degradation of extracellular matrix in vitro. (4) Mechanistically, the mitogen-activated protein kinase/c-jun N-terminal kinase (MAPK/JNK) signaling pathway may be involved in the regulation of Nrg4 in the pathophysiology of OA. Therefore, we concluded that Nrg4 alleviated the progression of OA by inhibiting the inflammation, protecting against apoptosis of chondrocyte, and decreasing the degradation of extracellular matrix in a manner involving MAPK/JNK signaling.

• Publisher: Springer Nature B.V
• Subject: Apoptosis / Arthritis / c-Jun protein / Cartilage (articular) / Cartilage diseases / Chondrocytes / Collagen (type II) / Degradation / Diabetes mellitus (non-insulin dependent) / Extracellular matrix / Fatty liver / Inflammation / Inflammatory bowel diseases / JNK protein / Kinases / Liver diseases / MAP kinase / Neuregulin / Osteoarthritis / Pathophysiology / Protein kinase / Risk factors / Signal transduction / Transcription factors