Hydrostatic pressure as epigenetic modulator in chondrocyte cultures: A study on miRNA-155, miRNA-181a and miRNA-223 expression levels

Palma, Armando M. De; Cheleschi, Sara; Pascarelli, Nicola Antonio; Giannotti, Stefano; Gargiulo, Mauro; Fioravanti, Antonella

doi:10.1016/j.jbiomech.2017.10.044

Cited by 22 publications

(23 citation statements)

References 26 publications

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“…The expression of miR-181a-5p in human knee and hip is increased in OA compared with normal chondrocytes21 27. Thus, we investigated if miR-181a-5p was upregulated in degenerated OA cartilage of the knee, one of the most common joints affected by OA.…”

Section: Resultsmentioning

confidence: 99%

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints

et al. 2018

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ObjectivesWe recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration.MethodsWe used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression.ResultsmiR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects.ConclusionsOur data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.

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Section: Resultsmentioning

confidence: 99%

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints

et al. 2018

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“…Yet, specifically in cells derived from OA AC hydrostatic pressure downregulates miR-181 [211]. In human knee AC cell monolayer cultures transfection with miR-181 mimic decreases proliferation and increases apoptosis.…”

Section: Mirna Regulation Of Fibroblast Growth Factor 2 Transformmentioning

confidence: 99%

Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

Boehme,

Rolauffs

2018

IJMS

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Osteoarthritis (OA) is a degenerative whole joint disease, for which no preventative or therapeutic biological interventions are available. This is likely due to the fact that OA pathogenesis includes several signaling pathways, whose interactions remain unclear, especially at disease onset. Early OA is characterized by three key events: a rarely considered early phase of proliferation of cartilage-resident cells, in contrast to well-established increased synthesis, and degradation of extracellular matrix components and inflammation, associated with OA progression. We focused on the question, which of these key events are regulated by growth factors, inflammatory cytokines, and/or miRNA abundance. Collectively, we elucidated a specific sequence of the OA key events that are described best as a very early phase of proliferation of human articular cartilage (AC) cells and concomitant anabolic/catabolic effects that are accompanied by incipient pro-inflammatory effects. Many of the reviewed factors appeared able to induce one or two key events. Only one factor, fibroblast growth factor 2 (FGF2), is capable of concomitantly inducing all key events. Moreover, AC cell proliferation cannot be induced and, in fact, is suppressed by inflammatory signaling, suggesting that inflammatory signaling cannot be the sole inductor of all early OA key events, especially at disease onset.

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“…In the present study, HA/CNP for the delivery of curcuminoid was found to promote the expression of IκB. IκB is an inhibitor of the NF-κB pathway ( 21 ). Therefore, HA/CNP can be used to inhibit the NF-κB pathway by increasing IκB.…”

Section: Discussionmentioning

confidence: 69%

Therapeutic potential of hyaluronic acid/chitosan nanoparticles for the delivery of curcuminoid in knee osteoarthritis and an in�vitro evaluation in chondrocytes

et al. 2018

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Knee osteoarthritis (OA) is the main cause of leg pain in middle-aged and elderly individuals. Hyaluronic acid (HA), as well as curcuminoid, has been used in the treatment of knee OA. In the present study, HA/chitosan nanoparticles (CNPs) were prepared for the delivery of curcuminoid, in order to investigate whether HA and curcuminoid can act synergistically as a better treatment option. The knee OA model was established by the Hulth method, and a knee OA chondrocyte model was constructed by the co-induction of interleukin-1β and tumor necrosis factor (TNF)-α. The drug loading capacity of HA/CNP for the delivery of curcuminoid was measured by an ultraviolet assay, and the cytotoxicity to chondrocytes was measured by an MTT assay. Collagen II was detected by immunofluorescence, and the expression levels of nuclear factor (NF)-κB and inflammation-related genes in cartilage tissue and chondrocytes were detected. Chondrocyte proliferation was determined by an EdU assay, and chondrocyte apoptosis was determined by flow cytometry. The Mankin pathological score of the Outerbridge classification was obtained. The results demonstrated that the optimum drug loading capacity of HA/CNP for the delivery of curcuminoid was 38.44%, with a good sustained release function. HA/CNP treatment resulted in inhibition of the NF-κB pathway, as well as the expression of matrix metalloproteinase (MMP)-1 and MMP-13, but it increased collagen II expression. HA/CNP for the delivery of curcuminoid significantly decreased the Outerbridge classification and Mankin pathological scores to close to normal until the 4th week. Furthermore, it was also observed that all the effects of HA/CNP on the delivery of curcuminoid were more prominent compared with the effects of HA or curcuminoid treatment individually. Taken together, these findings demonstrated that HA/CNP for the delivery of curcuminoid may suppress inflammation and chondrocyte apoptosis in knee OA via repression of the NF-κB pathway.

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Hydrostatic pressure as epigenetic modulator in chondrocyte cultures: A study on miRNA-155, miRNA-181a and miRNA-223 expression levels

Cited by 22 publications

References 26 publications

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints

Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

Therapeutic potential of hyaluronic acid/chitosan nanoparticles for the delivery of curcuminoid in knee osteoarthritis and an in�vitro evaluation in chondrocytes

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