Small interfering RNAs in the management of human rheumatoid arthritis

Gargano, Giuseppe; Oliva, Francesco; Oliviero, Antonio; Maffulli, Nicola

doi:10.1093/bmb/ldac012

Cited by 70 publications

(45 citation statements)

References 55 publications

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“…In this context, GABRA1 mRNA and GABA A R α1 protein levels were examined in OA mice and the cartilage tissues of OA patients, which manifested decreased GABRA1 mRNA and GABA A R α1 protein levels. Of note, small interfering RNA [siRNA, one form of RNA interference (RNAi)]-induced gene dysregulation participates in the mediation of musculoskeletal conditions, such as tendon homeostasis and rheumatoid arthritis [40,41]. Like siRNAs, shRNAs, another form of RNAi, may be transfected as plasmid vectors encoding shRNAs transcribed by RNA pol III or modified pol II promoters [42].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis

Yuan¹,

Wu²,

Zhong³

et al. 2022

J Orthop Surg Res

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Objective This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism. Methods The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meniscus, followed by measurement of Gm37494, microRNA (miR)-181a-5p, GABRA1 mRNA, and the encoded GABAARα1 protein expression. Thereafter, a cellular model was induced by interleukin-1β (IL-1β) treatment in chondrocytes, followed by ectopic and silencing experiments. Chondrocyte proliferation was detected by CCK-8 and EdU assays, chondrocyte apoptosis by flow cytometry and western blot, and the levels of inflammatory factors by ELISA. The binding of Gm37494 to miR-181a-5p was evaluated by dual-luciferase reporter gene and RIP assays, and that of GABRA1 to miR-181a-5p by dual-luciferase reporter gene and RNA pull-down assays. Results OA patients and mice had decreased GABRA1 mRNA and GABAARα1 protein levels and elevated miR-181a-5p expression in cartilage tissues. Additionally, Gm37494 was poorly expressed in OA mice. Mechanistically, Gm37494 directly bound to and inversely modulated miR-181a-5p that negatively targeted GABRA1. In IL-1β-induced chondrocytes, Gm37494 overexpression enhanced cell proliferation and suppressed cell apoptosis and inflammation, whereas further miR-181a-5p up-regulation or GABRA1 silencing abolished these trends. Conclusions Conclusively, Gm37494 elevated GABRA1 expression by binding to miR-181a-5p, thus ameliorating OA-induced chondrocyte damage.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis

Yuan¹,

Wu²,

Zhong³

et al. 2022

J Orthop Surg Res

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“…Our study shows that EBLN3P promotes the metastasis and drug resistance of osteosarcoma through miR-200a-3p/OGT axis. The miRNAs also are closely related to the occurrence of bone-related diseases [ 8 , 9 , 36 ]. Acted as effective regulatory genes, miRNAs have been demonstrated binding their target gene such as ERK 2, TGF- β1, and Smad3 to regulate tendon homeostasis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…As an important epigenetic regulator, LncRNAs mainly regulate the expression of related functional proteins via miRNA [6]. And the miRNAbased therapies have great potential compared with traditional therapies for diseases treatment, including musculoskeletal diseases [7][8][9]. LncEBLN3P is a pseudogene of endogenous bornavirus-like nucleoprotein 3 (EBLN3) located on chromosome 9.…”

Section: Introductionmentioning

confidence: 99%

LncRNA EBLN3P attributes methotrexate resistance in osteosarcoma cells through miR-200a-3p/O-GlcNAc transferase pathway

Sun

Sun³

et al. 2022

J Orthop Surg Res

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Background Osteosarcoma is highly malignant. The migration, invasion, and chemoresistance contribute to poor prognosis of osteosarcoma. Research reported that endogenous bornavirus-like nucleoprotein 3 pseudogene (EBLN3P) promotes the progression of osteosarcoma. Methods In this study, the expression of EBLN3P in osteosarcoma tissue with different methotrexate (MTX) treatment responses was measured. Osteosarcoma cell lines with MTX resistance were constructed, and bioinformatic analysis was performed to explore the potential involved targets and pathways. Results Higher EBLN3P was associated with MTX resistance. Downregulation of LncEBLN3P decreased the MTX resistance of osteosarcoma cells by sponging miR-200a-3p, an important microRNA that affects epithelial-mesenchymal transition (EMT). The decreased miR-200a-3p resulted in the upregulation of its target gene O-GlcNAc transferase (OGT), which in turn promoted the EMT process of osteosarcoma cells. Further analysis confirmed that the loss of OGT and over-expression of miR-200a-3p could partly abolish the MTX resistance induced by LncEBLN3P. Conclusion LncEBLN3P is upregulated in osteosarcoma and increases the MTX resistance in osteosarcoma cells through downregulating miR-200a-3p, which in turn promoted the EMT process of osteosarcoma cells by increasing the OGT.

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“…Furthermore, based on the natural processes of regulation of eukaryotic genes. Small interfering RNAs (siRNAs) mediated gene silencing has been used to regulate tendon homeostasis and human rheumatoid arthritis [ 29 , 30 ]. Consistently, in present study, the functional role of miR-210-3p may introduce the idea of using miR-210-3p targeted silencing-modified cell or scaffolds for bone repair.…”

Section: Discussionmentioning

confidence: 99%

miR-210-3p suppresses osteogenic differentiation of MC3T3-E1 by targeting brain derived neurotrophic factor (BDNF)

et al. 2022

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Background and objective As an important mediator of intercellular interaction and formation of extracellular bone matrix, porous scaffolds are widely used for bone regeneration. Accumulating evidences demonstrate that microRNA are involved in the regulation of scaffolds-induced bone regeneration. Recently, we revealed that miR-210-3p was highly expressed during osteogenesis induced by HAG. In present study, we further explored the molecular mechanism underlying the effect of miR-210-3p on osteogenic differentiation. Materials and methods In this study, miR-210-3p mimics and inhibitors were synthesized and transfected into MC3T3-E1 cells to explore their effects on osteogenic differentiation. The expression of osteogenic marker (Alp and Runx2) were detected by real-time quantitative PCR (qRT-PCR) and western blotting. After osteogenesis induction for 7 days, Alp staining were used to detected osteoblast differentiation of MC3T3-E1 cells. CCK8 and Transwell assays were performed to detected cell proliferation and migration. Then, top ranking list of target genes of miR-210-3p obtained from TargetScan and the expression of BDNF were detected by qRT-PCR and ELISA. The relationship between miR-210-3p and BDNF was verified by luciferase report assay. Furthermore, the effect of BDNF on osteoblast differentiation was verified by transfecting siRNA or adding BDNF to the culture medium. Results MiR-210-3p mimics markedly suppress osteogenic differentiation, cell migration and cell proliferation of MC3T3-E; nevertheless, silencing of miR-210-3p dramatically enhanced MC3T3-E1 osteogenesis, cell migration and proliferation. Furthermore, luciferase reporter assay verified that brain derived neurotrophic factor (BDNF) is a directly target of miR-210-3p. Moreover, BDNF siRNA significantly decreased the expression levels of ALP and cell migration. The addition of BDNF partially rescued the inhibition of osteogenesis by miR-210-3p. Conclusion miR-210-3p inhibited the osteogenic differentiation via targeting BDNF. Our Results provide a promising target for regulating osteogenic differentiation.

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Small interfering RNAs in the management of human rheumatoid arthritis

Cited by 70 publications

References 55 publications

Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis

Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis

LncRNA EBLN3P attributes methotrexate resistance in osteosarcoma cells through miR-200a-3p/O-GlcNAc transferase pathway

miR-210-3p suppresses osteogenic differentiation of MC3T3-E1 by targeting brain derived neurotrophic factor (BDNF)

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