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

• Published in: Calcified tissue international Vol. 110; no. 1; pp. 131 - 142
• Main Authors: Shi, Lingfeng, Xu, Xiaoli, Meng, Biying, He, Kaiyue, Sun, Yin, Tong, Jiayue, Xu, Jinling, Cheng, Yangyang, Gan, Guosheng, Xiang, Guangda
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2022; Springer Nature B.V
• Subjects: Animals; Apoptosis; Arthritis; Biochemistry; Biomedical and Life Sciences; c-Jun protein; Cartilage diseases; Cartilage, Articular; Cell Biology; Cells, Cultured; Chondrocytes; Collagen (type II); Degradation; Diabetes mellitus (non-insulin dependent); Disease Progression; Endocrinology; Extracellular matrix; Fatty liver; Inflammation; Inflammatory bowel diseases; JNK protein; Kinases; Life Sciences; Liver diseases; MAP kinase; Mice; Neuregulin; Neuregulins - genetics; Original Research; Orthopedics; Osteoarthritis; Osteoarthritis - genetics; Pathophysiology; Protein kinase; Risk factors; Signal transduction; Transcription factors; Neuregulin 4; Inflammation; Chondrocyte; Articular cartilage; Osteoarthritis
• ISSN: 0171-967X; 1432-0827; 1432-0827
• DOI: 10.1007/s00223-021-00897-2

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.