International immunopharmacologyAug 12, 2019

Exendin-4 influences key cell signals in inflamed human ligament stem cells to encourage bone formation

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 15, 2026

Abstract

Exendin-4 (Ex-4) promotes osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in an inflammatory environment.

LPS treatment increased the proliferation of PDLSCs but inhibited their ability to differentiate into bone.
Ex-4 reversed the effects of LPS by decreasing PDLSC proliferation and enhancing osteogenic differentiation.
Ex-4 elevated levels of key osteogenic markers, including Runx2, ALP, and Osx, while reducing pro-inflammatory cytokines TNF-α and IL-6.
The treatment with Ex-4 inhibited the nuclear translocation of NF-κB/p65, which is involved in inflammatory responses.
Co-treatment with Ex-4 and LPS resulted in decreased expression of β-catenin in the nucleus, suggesting modulation of Wnt signaling.

Simplified

A major feature of chronic periodontitis (CP) is the damage and destruction of alveolar bone. Periodontal ligament stem cells (PDLSCs) can differentiate into bone and improve CP. Exendin-4 (Ex-4) has been shown to have anti-inflammatory mechanisms and can promote bone regeneration. However, the effects of Ex-4 on the osteogenic differentiation of PDLSCs in the inflammatory microenvironment remains uncharacterized. In this study, we assessed the effects of Ex-4 on PDLSCs stimulated with lipopolysaccharide (LPS) to mimic the inflammatory environment. PDLSCs proliferation was assessed through CCK-8 assays and osteogenic differentiation was measured using Alizarin Red staining. The anti-inflammatory and osteogenic mechanisms of Ex-4 were assessed by western blot, RT-PCR, ELISA and immunofluorescence. We found that LPS treatment promoted the proliferative capacity of PDLSCs and inhibited their osteogenic differentiation. However, Ex-4 reversed these effects through suppressing PDLSCs proliferation and promoting osteogenic differentiation. Ex-4 increased Runx2, ALP, and Osx levels and decreased TNF-α and IL-6 expression. Ex-4 also reduced the expression of IκBα and p-IκBα, and inhibited the nuclear translocation of NF-κB/p65. The expression of β-catenin decreased in nucleus after co-treatment of Ex-4 with LPS. Taken together, these data demonstrate that Ex-4 promotes PDLSCs osteogenic differentiation in the inflammatory microenvironment through regulating NF-κB and Wnt signaling.

Full Text

Full text is available at the source.

View Full Text ↗

Exendin-4 influences key cell signals in inflamed human ligament stem cells to encourage bone formation

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief