Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model

基于大鼠模型DNA甲基化和RNA测序数据整合分析颗粒物对肌腱愈合的影响及机制

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作者:Su-Yel Lee, Min-Hyeok Lee, Seong-Kyeong Jo, In-Ha Yoo, Boler-Erdene Sarankhuu, Hyun-Jin Kim, Yea-Eun Kang, Seong-Eun Lee, Tae-Yeon Kim, Moon-Hyang Park, Choong-Sik Lee, Seung-Yun Han, Ji-Hyun Moon, Ju-Young Jung, Geum-Lan Hong, Nam-Jeong Yoo, Eun-Sang Yoon, Jae-Kyu Choi, Ho-Ryun Won, Ji-Woong Son, J

Abstract

Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.

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