Objective: To investigate the effects of kaempferol (KAE) on lipopolysaccharide (LPS)-induced
inflammatory damage and osteogenic differentiation in human dental pulp stem cells (hDPSCs) by modulating the
Wnt/β-catenin signaling pathway. Methods: HDPSCs were exposed to LPS to establish an in vitro inflammatory
model. After 48 h of treatment with graded concentrations of KAE (0, 12.5, 25, 50, 100, 200 μmol/L), CCK-8
assay was used to detect cell proliferation activity to determine the optimal treatment concentration of kaempferol.
HDPSCs cells were divided into control group, LPS group, low-, medium-, and high-dose kaempferol groups
(KAE-L, KAE-M, KAE-H), and high-dose kaempferol+Wnt inhibitor DKK1 group (KAE-H+DKK1). Enzyme-linked
immunosorbent assay was utilized to detect changes in inflammat ory factors such as tumor necrosis factor -α (TNF-α),
interleukin (IL)-6, and IL-1β. Alkaline phosphatase (ALP) staining was adopted to detect cellular ALP activity.
Alizarin red staining was performed to observe the formation of mineralized nodules in cells. Western blotting was
employed to measure the expression of osteogenesis-related proteins including Runt related transcription factor 2
(RUNX2), osteocalcin (OCN), bone morphogenetic protein 2 (BMP2), and Wnt/β-catenin pathway-related proteins.
Results: Compared with the control group, the LPS group showed an obvious decrease in ALP activity, mineral
nodule count, and the protein levels of RUNX2, OCN, BMP2, Wnt3a, and β-catenin, while exhibiting a prominent
increase in TNF-α, IL-6, and IL-1β. Compared with the LPS group, the KAE-trea ted groups dose-dependently showed
a prominent increase in ALP activity, mineral nodule
count, and levels of RUNX2, OCN, BMP2, Wnt3a, and
β-catenin proteins, while demonstrating a significant
decrease in TNF-α, IL-6, and IL-1β levels. Comparedwith the KAE-H group, the KAE-H+DKK1 group showed a significant decrease in ALP activity, mineral nodule
count, and levels of RUNX2, OCN, BMP2, Wnt3a, and β-catenin proteins, while indicating a marked increase in
TNF-α, IL-6, and IL-1β levels. Conclusion: Kaempferol can alleviate LPS-induced inflammatory damage and inhibit
osteogenic differentiation in hDPSCs, possibly achieved through activation of the Wnt/β-catenin signaling pathway.