ArticleStem cell research & therapy2026
The enhanced osteogenic differentiation of human periodontal ligament stem cells and M2 polarization of macrophages may be mediated by EphB4/ephrinB2 signaling pathway: a study of their direct co-culture.
Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundPeriodontal tissue regeneration can be achieved by periodontal ligament stem cells (PDLSCs) through its regulating the immune system. However, the specific signal or molecular mechanism remains unreported. The interaction between MSCs and macrophages (Mφ) has been the focus of the research in recent years. The objective of this study is to examine the effect of direct co-culture of human periodontal ligament stem cells (hPDLSCs) and macrophages on the osteogenic differentiation of hPDLSCs and the polarization of macrophages, and to explore the potential involvement of the EphB4/ephrinB2 signaling pathway in the interaction of co-cultured hPDLSCs and macrophages.
methodshPDLSCs isolated from human periodontal ligament were co-cultured with non-activated M0 macrophages (M0-Mφ) induced from THP-1. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), alkaline phosphatase (ALP) staining and assay, as well as Alizarin red staining (ARS) were carried out to evaluate hPDLSCs osteogenic differentiation. qRT-PCR and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to detect the expression of macrophage polarization-related factors. Western Blot was utilized to detect the expression of EphB4, ephrinB2, ERK1/2 and STAT3.
resultsWhen M0-Mφ was directly co-cultured with hPDLSCs at a ratio of 5:1, the co-culture system significantly promoted the osteogenic differentiation of hPDLSCs, as demonstrated by enhanced ALP staining/activity, ARS mineralization and upregulated mRNA expression of osteogenic markers (RUNX2, ALP, OCN/BGLAP, and OPN/SPP1). Meanwhile, the co-culture system markedly increased anti-inflammatory factor expression (TGF-β1 and IL-10) and decreased the pro-inflammatory factors (TNF-α and IL-1β), indicating enhanced polarization of alternatively activated macrophages (M2-Mφ). The mRNA and protein expression of EphB4 and ephrinB2 showed a significant increase with the time extension of the two cells' co-culture. However, pharmacological interruption of EphB4/ephrinB2 signaling pathway was associated with a decrease of hPDLSC osteogenic differentiation, M2 macrophage polarization, and p-STAT3 expression in the co-culture system.
conclusionsOur data suggest a potential mediatory role for the EphB4/ephrinB2 pathway in the osteogenic differentiation of hPDLSCs and the polarization of M2-Mφ within the co-culture system. Its regulatory effect on the osteogenic differentiation of hPDLSCs may involve the STAT3 signaling pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.