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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.


Related in: MedlinePlus

MiR-210 protected chondrocytes through inhibiting NF-κB pathway.(a) The expression of IκBα and p65 was detected by western blotting; (b) Cell apoptosis was measured by FCM. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. control group; #P < 0.05 vs. LPS group.
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f4: MiR-210 protected chondrocytes through inhibiting NF-κB pathway.(a) The expression of IκBα and p65 was detected by western blotting; (b) Cell apoptosis was measured by FCM. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. control group; #P < 0.05 vs. LPS group.

Mentions: DR6 has been shown to activate NF-κB and induce cell apoptosis18. To investigate whether NF-κB signaling pathway was involved in the protective effect of miR-210, pyrrolidine dithiocarbamic acid (PDTC) which is an inhibitor of NF-κB was used in the study. As shown in Fig. 4a, LPS induced activation of NF-κB signaling pathway with the evidences of p65 induction and IκBα reduction, and the activation was inhibited by PDTC. The regulation of p65 and IκBα caused by LPS was also inhibited by miR-210 mimic and DR6 siRNA. In addition, cell apoptosis caused by LPS was attenuated by PDTC, DR6 siRNA and miR-210 mimic (Fig. 4b), suggesting that miR-210 targeted DR6 and protected chondrocytes from LPS by inhibiting activation of NF-κB signaling pathway.


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

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

MiR-210 protected chondrocytes through inhibiting NF-κB pathway.(a) The expression of IκBα and p65 was detected by western blotting; (b) Cell apoptosis was measured by FCM. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. control group; #P < 0.05 vs. LPS group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525484&req=5

f4: MiR-210 protected chondrocytes through inhibiting NF-κB pathway.(a) The expression of IκBα and p65 was detected by western blotting; (b) Cell apoptosis was measured by FCM. Data are shown as mean ± SD of three experimental replicates. *P < 0.05 vs. control group; #P < 0.05 vs. LPS group.
Mentions: DR6 has been shown to activate NF-κB and induce cell apoptosis18. To investigate whether NF-κB signaling pathway was involved in the protective effect of miR-210, pyrrolidine dithiocarbamic acid (PDTC) which is an inhibitor of NF-κB was used in the study. As shown in Fig. 4a, LPS induced activation of NF-κB signaling pathway with the evidences of p65 induction and IκBα reduction, and the activation was inhibited by PDTC. The regulation of p65 and IκBα caused by LPS was also inhibited by miR-210 mimic and DR6 siRNA. In addition, cell apoptosis caused by LPS was attenuated by PDTC, DR6 siRNA and miR-210 mimic (Fig. 4b), suggesting that miR-210 targeted DR6 and protected chondrocytes from LPS by inhibiting activation of NF-κB signaling pathway.

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