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Published on: March 18, 2022
Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice
Lingfeng Shi1, Xiaoli Xu1,2, Biying Meng2
1The First School of Clinical Medicine, Southern Medical University, No.1023, South Shatai Road, Baiyun District, Guangzhou, 510515, Guangdong, China.
Abstract:
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.
Insights
Neuregulin 4 (Nrg4) protects against osteoarthritis (OA) by reducing inflammation and chondrocyte apoptosis. Restoring Nrg4 alleviates cartilage damage, suggesting therapeutic potential for this protein in OA treatment.
Area of Science:
- Orthopedics
- Immunology
- Cell Biology
Background:
- Osteoarthritis (OA) involves chondrocyte apoptosis and extracellular matrix degradation.
- Inflammation is a key factor in OA pathogenesis.
- Neuregulin 4 (Nrg4) has shown protective roles in other inflammatory conditions.
Purpose of the Study:
- To investigate the role of Neuregulin 4 (Nrg4) in osteoarthritis (OA) progression.
- To determine if Nrg4 can mitigate OA-related cartilage damage and inflammation.
Main Methods:
- Evaluated the effects of Nrg4 deficiency and restoration in vivo.
- Assessed the impact of recombinant Nrg4 (rNrg4) on chondrocytes in vitro.
- Investigated the involvement of the MAPK/JNK signaling pathway.
Main Results:
- Nrg4 deficiency exacerbated articular cartilage destruction, inflammation, and chondrocyte apoptosis in vivo.
- Nrg4 restoration reversed these detrimental effects.
- rNrg4 suppressed chondrocyte inflammation and apoptosis and reduced extracellular matrix degradation in vitro.
- The MAPK/JNK signaling pathway was implicated in Nrg4's mechanism of action.
Conclusions:
- Nrg4 plays a protective role in OA.
- Nrg4 alleviates OA progression by inhibiting inflammation, chondrocyte apoptosis, and extracellular matrix degradation.
- Nrg4's effects involve the MAPK/JNK signaling pathway, indicating potential therapeutic targets.
