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Published on: March 15, 2018
Kir2.1 regulates peri-implant bone resorption by inhibiting Wnt/β-catenin signaling and increasing the RANKL/OPG
Cancan Zu1, Jiahong Shi1, Dina Hanati2
1Department of Periodontics, Nanjing Stomatological Hospital, Affiliated Hosptital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China; Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
Objective:
Kir2.1, an inwardly rectifying potassium channel, is implicated in bone metabolism and inflammatory responses. This work holds the objective of investigating its role in bone remodeling in osteoblasts under the inflammatory conditions of peri-implantitis (PI).
Design:
Kir2.1 expression was evaluated in human gingival and mice peri-implant tissues by immunohistochemistry. Mouse osteoblasts (MC3T3-E1) were stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g-LPS). The expression of Kir2.1, IL-6, RANKL, OPG, and Wnt/β-catenin pathway markers was evaluated using qRT-PCR and Western blot. After Kir2.1 inhibition or knockdown, ALP and ARS staining were measured to evaluate bone formation. Conditioned medium from osteoblasts following Kir2.1 knockdown was used to treat BMDMs, and subsequent osteoclast differentiation was evaluated by TRAP staining. β-catenin localization was detected by immunofluorescence.
Results:
Significant upregulation was observed for both Kir2.1 and IL-6 in PI tissues from both human patients and mice models compared to the healthy controls. In vitro, P.g-LPS upregulated Kir2.1 expression and increased the RANKL/OPG ratio in osteoblasts. Inhibiting or knock-down of Kir2.1 effectively lowered the RANKL/OPG ratio, enhanced matrix mineralization and reduced osteoclast differentiation. Furthermore, Kir2.1 knock-down triggered nuclear translocation of β-catenin, stimulating the activation of the Wnt/β-catenin signaling pathway which could partially regulate the RANKL/OPG balance.
Conclusion:
Kir2.1 plays a vital role in PI by regulating bone remodeling via the Wnt/β-catenin/RANKL-OPG axis. Targeted inhibition of Kir2.1 could offer a novel strategy to mitigate bone loss in PI.
Insights
Kir2.1 channels are crucial in peri-implantitis (PI) bone loss by influencing Wnt/β-catenin signaling. Inhibiting Kir2.1 may prevent bone resorption in PI.
Area of Science:
- Biomedical Engineering
- Oral Biology
- Immunology
Background:
- Kir2.1 (potassium channel subfamily K member 2) is linked to bone metabolism and inflammation.
- Peri-implantitis (PI) involves inflammation and bone loss around dental implants.
Purpose of the Study:
- To investigate the role of Kir2.1 in osteoblast bone remodeling during peri-implantitis.
- To explore Kir2.1's involvement in the Wnt/β-catenin/RANKL-OPG signaling pathway in PI.
Main Methods:
- Immunohistochemistry to assess Kir2.1 expression in human and mouse PI tissues.
- Stimulation of mouse osteoblasts with P.g-LPS and evaluation of gene/protein expression (Kir2.1, IL-6, RANKL, OPG, Wnt/β-catenin markers).
- Assessment of bone formation and osteoclast differentiation following Kir2.1 inhibition or knockdown.
Main Results:
- Kir2.1 and IL-6 were upregulated in PI tissues.
- P.g-LPS increased Kir2.1 and the RANKL/OPG ratio in osteoblasts.
- Kir2.1 inhibition/knockdown reduced the RANKL/OPG ratio, improved mineralization, and decreased osteoclast differentiation.
- Kir2.1 knockdown activated Wnt/β-catenin signaling, influencing the RANKL/OPG balance.
Conclusions:
- Kir2.1 significantly contributes to bone remodeling in PI through the Wnt/β-catenin/RANKL-OPG axis.
- Targeting Kir2.1 presents a potential therapeutic strategy to reduce bone loss in peri-implantitis.
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