Kir2.1 regulates peri-implant bone resorption by inhibiting Wnt/β-catenin signaling and increasing the RANKL/OPG ratio in osteoblasts.

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.