Osteoarthritis (OA) is a common inflammatory joint disease characterised by progressive cartilage destruction. Management of this condition remains a significant challenge, and new therapies are required. We investigated the protective effects of miR-106a mimics in a murine model of OA.

Material and methods:
This study was performed using both in vitro and in vivo OA models. Primary chondrocytes were isolated from female rats, with inflammation induced via treatment with lipopolysaccharide (LPS). Then the effects of a miR-106a mimic were examined based on the level of inflammatory cytokine production and apoptotic signalling following LPS stimulation. An in vivo rat model of OA was generated by injecting LPS into the anterior cruciate ligament, followed by treatment with miR-106a mimics. Then, inflammatory and apoptotic protein expression was assessed in the cartilage tissue.

Treatment with miR-106a mimic reduced the levels of inflammatory cytokines and apoptotic proteins in cartilage tissues following LPS-induced inflammation. Furthermore, the mimic ameliorated the expression of DR-6 mRNA and DR6, IκBα, and p65 proteins in chondrocytes. Similar effects were seen in the in vivo model, with the mimic attenuating expression of NF-κB, p65, IκBα, and DR6 proteins and improving histopathological outcomes in the chondrocytes of OA rats.

Treatment with miR-106a mimic ameliorates inflammation in cartilage tissues of OA subjects by activating death receptor 6 via the NF-κB signalling pathway.

Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64: 1697-707.
Qiao YQ, Jiang PF, Gao YZ. Lutein prevents osteoarthritis through Nrf2 activation and downregulation of inflammation. Arch Med Sci 2018; 14: 617-24.
Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis 2013; 5: 77-94.
Hwang HW, Mendell JT. MicroRNAs in cell proliferation, cell death, and tumourigenesis. Br J Cancer 2006; 94: 776-80.
Papanagnou P, Stivarou T, Tsironi M. The role of miRNAs in common inflammatory arthropathies: osteoarthritis and gouty arthritis. Biomolecules 2016; 6: 44.
Malemud CJ. MicroRNAs and osteoarthritis. Cells 2018; 7: 92.
Zhao J, Yue D, Zhou Y, et al. The role of microRNAs in Abeta deposition and tau phosphorylation in Alzheimer’s disease. Front Neurol 2017; 8: 342.
Huang Q, Ma Q. MicroRNA-106a inhibits cell proliferation and induces apoptosis in colorectal cancer cells. Oncol Lett 2018; 15: 8941-4.
Hoey C, Ray J, Jeon J, et al. miRNA-106a and prostate cancer radioresistance: a novel role for LITAF in ATM regulation. Mol Oncol 2018; 12: 1324-41.
Shen Y, Yu J, Jing Y, Zhang J. MiR-106a aggravates sepsis-induced acute kidney injury by targeting THBS2 in mice model. Acta Cir Bras 2019; 34: e201900602.
He Z, Jiang J, Kokkinaki M, et al. MiRNA-20 and mirna-106a regulate spermatogonial stem cell renewal at the post-transcriptional level via targeting STAT3 and Ccnd1. Stem Cells 2013; 31: 2205-17.
Micheau O, Lens S, Gaide O, Alevizopoulos K, Tschopp J. NF-kappaB signals induce the expression of c-FLIP. Mol Cell Biol 2001; 21: 5299-305.
Gartland A, Mechler J, Mason-Savas A, et al. In vitro chondrocyte differentiation using costochondral chondrocytes as a source of primary rat chondrocyte cultures: an improved isolation and cryopreservation method. Bone 2005; 37: 530-44.
Chen D, Shen J, Zhao W, et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res 2017; 5: 16044.
Arenas-Padilla M, Mata-Haro V. Regulation of TLR signalling pathways by microRNAs: implications in inflammatory diseases. Cent Eur J Immunol 2018; 43: 482-9.
Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm 2014; 2014: 561459.
Giridharan S, Srinivasan M. Mechanisms of NF-kappaB p65 and strategies for therapeutic manipulation. J Inflamm Res 2018; 11: 407-19.
Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 2009; 1: a000034.
Charlier E, Relic B, Deroyer C, et al. Insights on molecular mechanisms of chondrocytes death in osteoarthritis. Int J Mol Sci 2016; 17: 2146.
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