The TGF‑&beta;1/COX‑2‑dependant pathway serves a key role in the generation of OKC‑induced M2‑polarized macrophage‑like cells and angiogenesis

Cheng,Gang; Gao,Jinxing; Wang,Lianfei; Ding,Yude; Wu,Qian; Wang,Quanbing; Xiao,Jialing; Wang,Shibing

doi:10.3892/ol.2020.11900

The TGF‑β1/COX‑2‑dependant pathway serves a key role in the generation of OKC‑induced M2‑polarized macrophage‑like cells and angiogenesis

Authors:
- Gang Cheng
- Jinxing Gao
- Lianfei Wang
- Yude Ding
- Qian Wu
- Quanbing Wang
- Jialing Xiao
- Shibing Wang
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Affiliations: Department of Stomatology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Stomatology, Zhejiang Hospital, Hangzhou, Zhejiang 310014, P.R. China, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
Published online on: July 23, 2020 https://doi.org/10.3892/ol.2020.11900
Article Number: 39
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

An odontogenic keratocyst (OKC) is a common oral cyst arising from the odontogenic epithelium, which has the characteristics of a tumor. Previous studies have demonstrated that M2‑polarized macrophages and angiogenesis have important roles in the progression of OKCs. As transforming growth factor (TGF)‑β1 is important in growth and developmental processes, and early studies have indicated that TGF‑β1 is upregulated in OKCs, the present study aimed to investigate the expression levels of TGF‑β1 as a first step. Flow cytometric analysis suggested that TGF‑β1 induced M2‑polarization of macrophages in a dose‑dependent manner. Expression levels of cyclooxygenase (COX)‑1 and ‑2 were measured after treatment of M2 macrophages with TGF‑β1 and OKC homogenate supernatant. COX‑2 expression was influenced by TGF‑β1 in a concentration‑dependent manner and in OKC induction. In addition, inhibition of COX‑2 resulted in the induction of M2‑polarization of macrophages via TGF‑β1 and OKC disruption. Because the extracellular matrix (ECM) is altered in individuals with chronic diseases, the present study analyzed the expression of matrix metalloproteinase (MMP)‑9, which is able to degrade the ECM. The present study observed a decrease in MMP‑9 activity following treatment with TGF‑β1 and OKC homogenate supernatant. Additionally, the present study analyzed tube formation caused by OKC with or without a COX‑2 inhibitor. The results of the present study suggested that angiogenesis increased following treatment with OKC homogenate supernatant but decreased after treatment with a COX‑2 inhibitor. These findings indicated that the TGF‑β1/COX‑2 pathway may have an important role in the progression of OKC.

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