MiR-378 exaggerates angiogenesis and bone erosion in collagen-induced arthritis mice by regulating endoplasmic reticulum stress
Year: 2024
Type: article
Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by pain, inflammation, and discomfort in the synovial joints. It is critical to understand the pathological mechanisms of RA progression. MicroRNA-378 (miR-378) is highly expressed in the synovium of RA patients and positively correlated with disease severity, but its function and underlying mechanisms remain poorly understood. In this study, miR-378 transgenic (miR-378 high ) mice were used to construct the collagen-induced arthritis (CIA) model for exploring the role of miR-378 in RA development. miR-378 high CIA mice showed accelerated RA development, as evidenced by exaggerated joint swelling and bone structural deformities. More severe endoplasmic reticulum (ER) stress and the consequent angiogenesis and osteoclastogenesis were also activated in the synovial tissue and calcaneus, respectively, in the miR-378 high group, suggesting that ER plays a significant role in miR-378-mediated RA pathogenesis. Upon in vitro RA induction, fibroblast-like synoviocytes (FLSs) isolated from miR-378 high mice showed a higher expression level of ER stress markers. The conditioned medium (CM) from RA-FLSs of miR-378 high mice stimulated more intensive angiogenesis and osteoclastogenesis. The ER stress-related protein Crebrf was identified as a downstream target of miR-378. Crebrf knockdown diminished the promoting effect of miR-378 on ER stress, as well as its downstream angiogenesis and osteoclastogenesis activities. Tail vein injection of anti-miR-378 lentivirus in an established RA mouse model was shown to ameliorate RA progression. In conclusion, miR-378 amplified RA development by promoting ER stress and downstream angiogenesis and osteoclastogenesis, thus indicating that miR-378 may be a potential therapeutic target for RA treatment.
Source: Cell Death and Disease
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,790
Funders: National Natural Science Foundation of China, Research Grants Council, University Grants Committee, Innovation and Technology Commission, Chinese University of Hong Kong, Food and Health Bureau, Health and Medical Research Fund, National Natural Science Foundation of China-Yunnan Joint Fund
Awards: G1312947998, G1321987127, Effect of sesamin on promoting osteoprotic fracture healing, G283911285, Functionalization of Wnt5a biomimetic peptide on biomaterials for enhanced bone regeneration and implant osseointegration, G3210027332, Mechanistic studies of tibial cortex transverse transport (TTT) surgery in improving diabetic foot ulcers healing outcomes, G4327872768, G4685367558, G4866978311, G4868188824, G5336223502, Engineering the biomimetic structural and mechanical heterogeneity of cell-adaptable nanocomposite hydrogels for biomedical applications, G6979233706, G7210440535, G7413394314, The Role of Lgr5 in Cartilage Development and Mesenchymal Stem Cells Mediated Cartilage Repair, Development of staphylococcal enterotoxins C2 (SEC2) as a drug to promote osteoporotic fracture healing, G8769384380, Mechanistic Studies on Treatment of Diabetic Foot Ulcers by Novel Tibial Cortex Transverse Transport Surgery
OpenAlex ID: W4405524910