Cathelicidin antimicrobial peptide (CAMP) gene promoter methylation induces chondrocyte apoptosis

Guoliang Wang,Lu He,Yang Wang,Tengyun Yang,Yanlin Li,Guang Yang

doi:10.1186/s40246-021-00321-8

Abstract

ObjectiveThe occurrence of osteoarthritis is related to genetic and environmental factors. Among them, the change of chondrocyte gene expression pattern regulated by epigenetic modification is an important participant. This study analyzed the effect of CAMP gene methylation on the level of oxidative stress and inflammation of chondrocytes.MethodsWe analyzed the changes of the transcriptome in the articular cartilage tissue of osteoarthritis (OA) patients from the GSE117999 dataset. The GSE48422 dataset was used to analyze the changes in the methylation level of osteoarthritis cells. Cell Counting Kit-8 (CCK-8) and flow cytometry analysis of short hairpin RNA (shRNA) silencing CAMP gene and 5-μM 5-Aza-2’-Deoxycytidine (AZA) treatment on the proliferation and apoptosis of Human chondrocytes osteoarthritis (HC-OA) cells. The Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect the level of reactive oxygen species (ROS), and the expression level of inflammatory factors was analyzed by Western Blot.ResultsThe expression of CAMP in cartilage tissue of OA patients was upregulated, and the level of methylation was downregulated. CAMP was highly expressed in osteoarthritis articular cartilage cells. Silencing CAMP inhibited the proliferation of HC-OA cells and promoted their apoptosis. CAMP gene methylation inhibited ROS levels and tumor necrosis factor-α (TNF-α) expression levels in HC-OA cells, and promoted transforming growth factor beta (TGF-β) expression. CAMP gene methylation inhibited the proliferation of HC-OA cells and promoted their apoptosis.ConclusionCAMP gene promoter methylation inhibits ROS levels and inflammation and induces chondrocyte apoptosis.

Highlights

Osteoarthritis (OA) is a common age-related degenerative disease
The expression of CAMP in cartilage tissue of OA patients was upregulated, and the level of methylation was downregulated The analysis of the GSE117999 dataset shows that CAMP was upregulated in the articular cartilage of patients with OA (Table 1, Fig. 1a)
CAMP was highly expressed in osteoarthritis articular cartilage cells We analyzed the expression levels of CAMP in the cartilage tissue of 8 cases of OA patients undergoing total knee arthroplasty and 5 cases of trauma requiring high amputation (Control)

Summary

Introduction

Osteoarthritis (OA) is a common age-related degenerative disease. Research in recent years has shown that epigenetic modification plays an important role in the pathogenesis of OA [4, 5]. Epigenetic modification mainly includes DNA methylation, histone modification, chromatin remodeling, and non-coding RNA, among which DNA methylation is closely related to inflammatory diseases [6, 7]. DNA methylation studies of OA mainly focus on articular cartilage, because articular cartilage is the core tissue involved in the disease process [8]. DNA methylation has become an important regulator of chondrocyte dedifferentiation, severely destroying the results of autologous chondrocyte implantation in patients with cartilage injury [8]. It is of great significance to study the DNA methylation profile of chondrocyte dedifferentiation

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Results

Conclusion