Regulation of inflammatory and catabolic responses to IL-1β in rat articular chondrocytes by microRNAs miR-122 and miR-451
| Autor: | Zvi Schwartz, Brian D. Snyder, Madeline Hays, Mark W. Grinstaff, Taylor B. Lawson, David Josh Cohen, Kayla M. Scott, Barbara D. Boyan, D.W. Nielson |
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| Rok vydání: | 2021 |
| Předmět: |
Cartilage
Articular 0301 basic medicine medicine.medical_specialty Anterior cruciate ligament Interleukin-1beta Oligonucleotides Biomedical Engineering Endogeny Inflammation Osteoarthritis In Vitro Techniques Matrix (biology) Dinoprostone 03 medical and health sciences Chondrocytes 0302 clinical medicine Rheumatology Internal medicine Matrix Metalloproteinase 13 medicine MiR-122 Animals Orthopedics and Sports Medicine 030203 arthritis & rheumatology Chemistry Anterior Cruciate Ligament Injuries Osteoarthritis Knee medicine.disease Arthritis Experimental In vitro Rats MicroRNAs 030104 developmental biology Endocrinology medicine.anatomical_structure Lipofectamine Cytokines medicine.symptom |
| Zdroj: | Osteoarthritis and Cartilage. 29:113-123 |
| ISSN: | 1063-4584 |
| DOI: | 10.1016/j.joca.2020.09.004 |
| Popis: | Summary Objective miR-122 stimulates proliferation of growth plate chondrocytes whereas miR-451 stimulates terminal differentiation and matrix turnover. Here, we examined the potential of these microRNA as regulators of articular chondrocytes using an in vitro model of osteoarthritis. Methods miR-122 and miR-451 presence in rat articular cartilage was assessed using the anterior cruciate ligament transection model of OA. In vitro testing used first passage rat articular chondrocytes (rArCs) that were transfected with lipofectamine (Lipo) and miR-122 or miR-451 for 24-h, then treated with 10 ng/mL IL-1β in order to mimic an osteoarthritic environment. Conditioned media were collected and MMP13, PGE2 and OA-related cytokines were measured. Matrix vesicles were collected from cell layer lysates using ultra-centrifugation. Cells were treated with miR-122 or miR-451 inhibitors to verify miR-specific effects. Results Both miR-122 and miR-451 were increased in the OA articular cartilage compared to healthy tissue; rArCs expressed both microRNAs in MVs. miR-122 prevented IL-1β-dependent increases in MMP-13 and PGE2, whereas miR-451 significantly increased the IL-1β effect. Multiplex data indicated that miR-122 reduced the stimulatory effect of IL-1β on IL-1α, IL-2, Il-4, IL-6, GM-CSF, MIP-1A, RANTES and VEGF. In contrast, IL-2, IL-4, IL-6, GM-CSF, and MIP-1A were increased by miR-451 while VEGF was decreased. Inhibiting miR-122 exacerbated the response to IL-1β indicating endogenous levels of miR-122 were present. There were no differences in MMP-13 or PGE2 with miR-451 Locked Nucleic Acid (LNA) inhibitor treatment. Conclusions Both miRs were elevated in OA in a rat bilateral anterior cruciate ligament transection (ACLT) model. miR-122 prevented, while miR-451 exacerbated the effects of IL-1β on rArCs. |
| Databáze: | OpenAIRE |
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