Mechanism underlying carvacrol-induced alveolar bone repair via the phosphatidylinositol 3-kinase pathway in periodontal disease

doi:10.7518/hxkq.2025.2025050

Abstract

Abstract:

Objective This study aims to explore the mechanism of carvacrol (CV) in regulating alveolar bone repair in periodontal disease. Methods A rat model of periodontal disease (P group) was created by ligating the first molar and injecting lipopolysaccharide (LPS). A control model (C group) was also created. The treatment models received low (L group), medium (M group), and high (H group) doses of CV hydrogel. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in periodontal tissues. Immunohistochemical staining was employed to analyze the expression of collagen typeⅠ(COL1) and Runt-related transcription factor 2 (Runx2). In vitro, the rat osteoblast cells were divided into C, P, L, M, H, CV and CV+LY294002 (CV+LY) groups. Western blot analysis detected the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK-3β) pathway-related and osteoblastic proteins. Quantitative reverse-transcription po-lymerase chain reaction was used to measure the expression of inflammatory factors and osteoblastic proteins. The alkaline phosphatase (ALP) colorimetric kit and alizarin red S staining kit were utilized to assess osteogenic ability. Immunofluorescence (IF) was used to detect COL1 expression in osteoblasts. Transmission electron microscopy was applied to detect cell apoptosis. Results CV hydrogel alleviated periodontal symptoms, upregulated PI3K/AKT/GSK-3β pathway-related and osteoblastic proteins, and increased the expression of ALP and the number of calcified nodules. However, it decreased cell apoptosis and inflammatory factors. LY294002 inhibited the PI3K/AKT pathway and decreased osteoblastic protein expression, ALP coloration, and calcified nodule quantity. Conclusion CV hydrogel promotes the proliferation and differentiation of alveolar bone osteoblasts by activating the PI3K pathway and inhibiting inflammation-induced bone resorption. This study emphasizes the potential of CV for the treatment of periodontal diseases.

Key words: carvacrol, periodontal disease, osteoblasts, phosphatidylinositol 3-kinase, lipopolysaccharide

CLC Number:

R781.4

Teng Nian, Li Zhaoxun, Gao Tiantian, Xiang Yanrui, Zhou Lulu, Gao Xiang. Mechanism underlying carvacrol-induced alveolar bone repair via the phosphatidylinositol 3-kinase pathway in periodontal disease[J]. West China Journal of Stomatology, 2026, 44(1): 94-105.

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NCBI Reference Sequence	基因	引物（5’-3’）	长度/bp
XM_006253120.5	ALP	F：TGCACGACAATCGGGATGAA	20/20
		R：TAGTAACCGGAGCCCTCACA
NM_053304.1	COL1	F：GGTCTTGGTGGTTTTGTATTCG	22/21
		R：AACAGTCGCTTCACCTACAGC
XM_017596552.3	Runx2	F：TGGCCGGGAATGATGAGAAC	20/20
		R：GCTCCGGCCTACAAATCTCA
XM_063272870.1	OPN	F：CCAGCCAAGGACCAACTACA	20/20
		R：AGTGTTTGCTGTAATGCGCC
NM_031512.2	IL-1β	F：GCTTCCTTGTGCAAGTGTC	19/19
		R：TGGACAGCCCAAGTCAAGG
NM_012589.2	IL-6	F：GTTTCTCTCCGCAAGAGACTTC	22/20
		R：TGTGGGTGGTATCCTCTGTG
XM_063287055.1	COX-2	F：CGCAAATACTGCAGCCCTAC	20/20
		R：GGATGTCTTGTTCGTCTGCC
NM_012675.3	TNF-α	F：GGGTGATCGGTCCCAACAAG	20/19
		R：GCTTGGTGGTTTGCTACGA
NM_031144.3	β-actin	F：CTATCGGCAATGAGCGGTTCC	21/22
		R：GCACTGTGTTGGCATAGAGGTC

组别	SBI	PD/mm
C	0.60±0.52	0.21±0.05
P	2.80±0.42^A	0.90±0.17^A
L	2.22±0.44^a	0.76±0.13^A
M	1.91±0.54	0.69±0.15^a
H	1.20±0.63^b	0.41±0.15^B

组别	COL1	Runx2
C	95.30±4.45^b	96.35±2.35^b
P	11.81±4.48	17.98±2.03
L	34.14±7.61	73.61±8.21
M	63.76±2.64	89.32±7.70
H	72.17±5.27^b	96.34±3.67^b