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MiR-210 inhibits NF-κB signaling pathway by targeting DR6 in osteoarthritis.

Zhang D, Cao X, Li J, Zhao G - Sci Rep (2015)

Bottom Line: In the in vitro study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS).MiR-210 expression is reduced in OA rats.The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-κB signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

ABSTRACT
Osteoarthritis (OA) is characterized by degradation of articular cartilage and joint inflammation. MicroRNAs have been proved to play an important role in the regulation of chondrogenesis. Previous study showed that microRNA-210 (miR-210) was probably associated with osteoarthritis, while the function of miR-210 in osteoarthritis still remains unknown. The aim of the present study was to investigate the protective effect of miR-210 on osteoarthritis. In the in vitro study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS). Transfection with miR-210 mimic inhibited LPS-induced pro-inflammatory cytokines production, cell viability reduction and cell apoptosis. Results of luciferase activity assay showed that miR-210 targeted 3'-UTR of death receptor 6 (DR6) to inhibit its expression. MiR-210 mimic and DR6 siRNA transfection inhibited the activation of NF-κB pathway and cell apoptosis of chondrocytes. For the in vivo study, OA model was established on rats by anterior cruciate ligament transection (ACLT). MiR-210 expression is reduced in OA rats. MiR-210 over-expressing lentivirus was injected into the OA rats. Cytokines production, and NF-κB and DR6 expression in OA rats was inhibited by miR-210 overexpression. The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-κB signaling pathway.

No MeSH data available.


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Effect of miR-210 in OA rats.(a) The mRNA level of miR-210 in articular cartilages was detected by RT-PCR; (b–d) inflammatory factors in SF samples were measured by ELISA; (e) The expression of DR6, IκBα and p65 in articular cartilages was detected by western blotting; (f) the quantitative data for e. Data are shown as mean ± SD of five rats in each group. NC, normal control group; SS, sham surgery group; OA, OA model group; OA+miR-210, OA model with the treatment of miR-210-expressing lentivirus. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. normal control group; #P < 0.05 vs. sham surgery group; aP < 0.05 vs. OA model group.
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f5: Effect of miR-210 in OA rats.(a) The mRNA level of miR-210 in articular cartilages was detected by RT-PCR; (b–d) inflammatory factors in SF samples were measured by ELISA; (e) The expression of DR6, IκBα and p65 in articular cartilages was detected by western blotting; (f) the quantitative data for e. Data are shown as mean ± SD of five rats in each group. NC, normal control group; SS, sham surgery group; OA, OA model group; OA+miR-210, OA model with the treatment of miR-210-expressing lentivirus. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. normal control group; #P < 0.05 vs. sham surgery group; aP < 0.05 vs. OA model group.

Mentions: To investigate the role of miR-210 in vivo, the rat model of OA was built by anterior cruciate ligament transection (ACLT) in the right knees. MiR-210-expressing lentivirus was injected into articular cavity of the OA rats. On the 20 th day after the operation, the rats were sacrificed and the articular cartilages of medial tibial plateau and SF samples were collected for analysis. As shown in Fig. 5a, miR-210 level in the articular cartilages was decreased by 0.8-fold in OA rats and increased by 5.4-fold in lentivirus infected rats. Levels of the inflammatory cytokines in SF samples were measured by ELISA. Levels of IL-1β, IL-6 and TNF-αwere significantly increased by 3, 2.5, 1.5, 1.7, 1.8 and 1.5 fold in OA rats compared with sham surgery group. However, miR-210 overexpression inhibited the production of cytokines in SF samples (Fig. 5b–d). Expression of IκBα and p65 in OA rats were changed compared with sham surgery group (P < 0.05), while the effect could be inhibited by miR-210 overexpression (Fig. 5e,f).


MiR-210 inhibits NF-κB signaling pathway by targeting DR6 in osteoarthritis.

Zhang D, Cao X, Li J, Zhao G - Sci Rep (2015)

Effect of miR-210 in OA rats.(a) The mRNA level of miR-210 in articular cartilages was detected by RT-PCR; (b–d) inflammatory factors in SF samples were measured by ELISA; (e) The expression of DR6, IκBα and p65 in articular cartilages was detected by western blotting; (f) the quantitative data for e. Data are shown as mean ± SD of five rats in each group. NC, normal control group; SS, sham surgery group; OA, OA model group; OA+miR-210, OA model with the treatment of miR-210-expressing lentivirus. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. normal control group; #P < 0.05 vs. sham surgery group; aP < 0.05 vs. OA model group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f5: Effect of miR-210 in OA rats.(a) The mRNA level of miR-210 in articular cartilages was detected by RT-PCR; (b–d) inflammatory factors in SF samples were measured by ELISA; (e) The expression of DR6, IκBα and p65 in articular cartilages was detected by western blotting; (f) the quantitative data for e. Data are shown as mean ± SD of five rats in each group. NC, normal control group; SS, sham surgery group; OA, OA model group; OA+miR-210, OA model with the treatment of miR-210-expressing lentivirus. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. normal control group; #P < 0.05 vs. sham surgery group; aP < 0.05 vs. OA model group.
Mentions: To investigate the role of miR-210 in vivo, the rat model of OA was built by anterior cruciate ligament transection (ACLT) in the right knees. MiR-210-expressing lentivirus was injected into articular cavity of the OA rats. On the 20 th day after the operation, the rats were sacrificed and the articular cartilages of medial tibial plateau and SF samples were collected for analysis. As shown in Fig. 5a, miR-210 level in the articular cartilages was decreased by 0.8-fold in OA rats and increased by 5.4-fold in lentivirus infected rats. Levels of the inflammatory cytokines in SF samples were measured by ELISA. Levels of IL-1β, IL-6 and TNF-αwere significantly increased by 3, 2.5, 1.5, 1.7, 1.8 and 1.5 fold in OA rats compared with sham surgery group. However, miR-210 overexpression inhibited the production of cytokines in SF samples (Fig. 5b–d). Expression of IκBα and p65 in OA rats were changed compared with sham surgery group (P < 0.05), while the effect could be inhibited by miR-210 overexpression (Fig. 5e,f).

Bottom Line: In the in vitro study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS).MiR-210 expression is reduced in OA rats.The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-κB signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

ABSTRACT
Osteoarthritis (OA) is characterized by degradation of articular cartilage and joint inflammation. MicroRNAs have been proved to play an important role in the regulation of chondrogenesis. Previous study showed that microRNA-210 (miR-210) was probably associated with osteoarthritis, while the function of miR-210 in osteoarthritis still remains unknown. The aim of the present study was to investigate the protective effect of miR-210 on osteoarthritis. In the in vitro study, miR-210 level in chondrocytes was decreased after treatment with lipopolysaccharide (LPS). Transfection with miR-210 mimic inhibited LPS-induced pro-inflammatory cytokines production, cell viability reduction and cell apoptosis. Results of luciferase activity assay showed that miR-210 targeted 3'-UTR of death receptor 6 (DR6) to inhibit its expression. MiR-210 mimic and DR6 siRNA transfection inhibited the activation of NF-κB pathway and cell apoptosis of chondrocytes. For the in vivo study, OA model was established on rats by anterior cruciate ligament transection (ACLT). MiR-210 expression is reduced in OA rats. MiR-210 over-expressing lentivirus was injected into the OA rats. Cytokines production, and NF-κB and DR6 expression in OA rats was inhibited by miR-210 overexpression. The results demonstrated that miR-210 decreased inflammation in articular cavity in OA rats by targeting DR6 and inhibiting NF-κB signaling pathway.

No MeSH data available.


Related in: MedlinePlus