High expression of MAPK-14 promoting the death of chondrocytes is an important signal of osteoarthritis process

Abstract

Background Osteoarthritis (OA) is one of the most common degenerative diseases worldwide. Many researchers are studying the pathogenesis of OA, however, it is still unclear. Methods Screening and validation of OA relevant hub genes are an important part of exploring their potential molecular mechanism. Therefore, this study aims to explore and verify the mechanisms of hub genes in the OA by bioinformatics, qPCR, fluorescence and propidium iodide staining. Results Microarray datasets GSE43923, GSE55457 and GSE12021 were collected in the Gene Expression Omnibus (GEO), including 45 samples, which divided into 23 osteoarthritis knee joint samples and 22 samples of normal knee joint. Thereafter, 265 differentiallyexpressedgenes (DEGs) were identified in all, which divided into 199 upregulated genes and 66 downregulated genes. The hub genes MAPK-14, PTPRC, PTPN12 were upregulated, while B9D1 was downregulated. In order to further confirm the expression of screening differential genes in human chondrocytes, the human chondrocytes were extracted from a joint replacement surgery and stained with toluidine blue for identification. Compared with normal chondrocytes, OA chondrocytes had high expression of COL I protein and low expression of COL II protein. The expression levels of MAPK-14, PTPRC and PTPN12 in OA chondrocytes were significantly higher than the expression levels of B9D1 in normal chondrocytes. Moreover, the inflammatory necrosis of OA chondrocytes was increased compared with the normal chondrocytes by propidium iodide staining. Conclusions The high expression of MAPK-14 works as a promoter of chondrocytes death and an important signal of the osteoarthritis process.

The Homeostasis of Cartilage Matrix Remodeling and the Regulation of Volume-Sensitive Ion Channel

“…We recently confirmed that increased expression of COL I, decreased expression of COL II, a disordered cytoskeletal protein distribution, and loss of cell membrane integrity are important characteristics of OA, indicative of a decrease of anabolism of human OA chondrocytes [ 7 ]. We also confirmed that high expression of MAPK-14 may promote chondrocyte death [ 8 ]. Another study found that among several important proteoglycan proteases involved in matrix catabolism, the expression levels of MMP and aggrecanases (ADAMTs) are significantly higher in OA synovial fluid and joint tissues.…”

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

“…Makino that has many pharmacological functions, such as anti-inflammatory ( Lin et al, 2020 ; Wang et al, 2021b ), anti-tumor ( Han et al, 2011 ; He et al, 2013a ; He et al, 2013b ; He et al, 2014 ; Kang et al, 2016 ), anti-fungal, anti-cough, and analgesic activities. The MAPK, together with NF-κB signaling pathway, is thought to play crucial roles in the development of OA, as activation of these two pathway causes cartilage inflammation and damage ( Lianxu et al, 2006 ; Lepetsos et al, 2019 ; Chuntakaruk et al, 2021 ; Deng et al, 2021 ). Therefore, inhibition of these pathways may be a method of OA treatment ( Wu et al, 2020 ).…”

Chelidonine reduces IL-1β-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats

“…In addition, such inflammatory factors can combine with receptors on the articular cartilage surface to activate the NF-κB, p38 MAPK, JNK, and ERK1/2 pathways in chondrocytes. They can also induce MMPs production for proteoglycan and collagen degradation in cartilage ( 33 - 35 ). The NF-κB pathway accounts for an important regulating factor for chondrocyte inflammation ( 36 , 37 ), and its activation plays a key role in producing inflammatory factors like iNOS and COX-2 ( 38 ).…”