MicroRNA-375 exacerbates knee osteoarthritis through repressing chondrocyte autophagy by targeting ATG2B

This study aimed to explore the underlying mechanism of miR-375 in exacerbating osteoarthritis (OA). MiR-375 expression were upregulated in OA cartilage tissues, whereas ATG2B expression was decreased. MiR-375 targeted ATG2B 3' UTR and inhibited its expression in the chondrocytes, and then supp...

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Veröffentlicht in:Aging (Albany, NY.) NY.), 2020-04, Vol.12 (8), p.7248-7261
Hauptverfasser: Li, Hongxing, Li, Zhiling, Pi, Yigang, Chen, Yang, Mei, Lin, Luo, Yong, Xie, Jingping, Mao, Xinzhan
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container_issue 8
container_start_page 7248
container_title Aging (Albany, NY.)
container_volume 12
creator Li, Hongxing
Li, Zhiling
Pi, Yigang
Chen, Yang
Mei, Lin
Luo, Yong
Xie, Jingping
Mao, Xinzhan
description This study aimed to explore the underlying mechanism of miR-375 in exacerbating osteoarthritis (OA). MiR-375 expression were upregulated in OA cartilage tissues, whereas ATG2B expression was decreased. MiR-375 targeted ATG2B 3' UTR and inhibited its expression in the chondrocytes, and then suppressed autophagy and promoted endoplasmic reticulum stress (ERs). The apoptosis rate of chondrocytes was increased after being transfected with miR-375 mimics. results further verified that inhibition of miR-375 could relieve OA-related symptoms. miR-375 can inhibit the expression of ATG2B in chondrocytes, suppress autophagy and promote the ERs. It suggests that miR-375 could be considered to be a key therapy target for OA. Differential expression analyses for mRNA and miRNA microarray datasets from ArrayExpress were performed. MiR-375 and ATG2B expressions in cartilage tissues were detected by qRT-PCR. Dual luciferase assay was applied to verify the targeting relationship between ATG2B and miR-375. , the role of miR-375 on chondrocyte autophagy and ERs was investigated by western blot and immunofluorescence. The apoptotic rate was quantified by flow cytometry. , OA mice model was established, HE and Safranin O and Fast Green staining, as well as the OARSI and modified Mankin scores, were applied to measure the OA cartilage damage severity.
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MiR-375 expression were upregulated in OA cartilage tissues, whereas ATG2B expression was decreased. MiR-375 targeted ATG2B 3' UTR and inhibited its expression in the chondrocytes, and then suppressed autophagy and promoted endoplasmic reticulum stress (ERs). The apoptosis rate of chondrocytes was increased after being transfected with miR-375 mimics. results further verified that inhibition of miR-375 could relieve OA-related symptoms. miR-375 can inhibit the expression of ATG2B in chondrocytes, suppress autophagy and promote the ERs. It suggests that miR-375 could be considered to be a key therapy target for OA. Differential expression analyses for mRNA and miRNA microarray datasets from ArrayExpress were performed. MiR-375 and ATG2B expressions in cartilage tissues were detected by qRT-PCR. Dual luciferase assay was applied to verify the targeting relationship between ATG2B and miR-375. , the role of miR-375 on chondrocyte autophagy and ERs was investigated by western blot and immunofluorescence. The apoptotic rate was quantified by flow cytometry. , OA mice model was established, HE and Safranin O and Fast Green staining, as well as the OARSI and modified Mankin scores, were applied to measure the OA cartilage damage severity.</description><identifier>ISSN: 1945-4589</identifier><identifier>EISSN: 1945-4589</identifier><identifier>DOI: 10.18632/aging.103073</identifier><identifier>PMID: 32335541</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>Animals ; Apoptosis ; Autophagy - genetics ; Autophagy-Related Proteins - biosynthesis ; Autophagy-Related Proteins - genetics ; Cells, Cultured ; Chondrocytes - metabolism ; Chondrocytes - pathology ; Disease Models, Animal ; DNA Mutational Analysis ; Gene Expression Regulation ; Humans ; Male ; Mice ; MicroRNAs - biosynthesis ; MicroRNAs - genetics ; Osteoarthritis, Knee - genetics ; Osteoarthritis, Knee - metabolism ; Osteoarthritis, Knee - pathology ; Research Paper ; RNA, Messenger - genetics ; Signal Transduction ; Vesicular Transport Proteins - biosynthesis ; Vesicular Transport Proteins - genetics</subject><ispartof>Aging (Albany, NY.), 2020-04, Vol.12 (8), p.7248-7261</ispartof><rights>Copyright © 2020 Li et al.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-372abc8965b83a7dd23ca4ead1a165443728e1b630429f25a3bf1c66d451648c3</citedby><cites>FETCH-LOGICAL-c387t-372abc8965b83a7dd23ca4ead1a165443728e1b630429f25a3bf1c66d451648c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202526/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202526/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32335541$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Hongxing</creatorcontrib><creatorcontrib>Li, Zhiling</creatorcontrib><creatorcontrib>Pi, Yigang</creatorcontrib><creatorcontrib>Chen, Yang</creatorcontrib><creatorcontrib>Mei, Lin</creatorcontrib><creatorcontrib>Luo, Yong</creatorcontrib><creatorcontrib>Xie, Jingping</creatorcontrib><creatorcontrib>Mao, Xinzhan</creatorcontrib><title>MicroRNA-375 exacerbates knee osteoarthritis through repressing chondrocyte autophagy by targeting ATG2B</title><title>Aging (Albany, NY.)</title><addtitle>Aging (Albany NY)</addtitle><description>This study aimed to explore the underlying mechanism of miR-375 in exacerbating osteoarthritis (OA). MiR-375 expression were upregulated in OA cartilage tissues, whereas ATG2B expression was decreased. MiR-375 targeted ATG2B 3' UTR and inhibited its expression in the chondrocytes, and then suppressed autophagy and promoted endoplasmic reticulum stress (ERs). The apoptosis rate of chondrocytes was increased after being transfected with miR-375 mimics. results further verified that inhibition of miR-375 could relieve OA-related symptoms. miR-375 can inhibit the expression of ATG2B in chondrocytes, suppress autophagy and promote the ERs. It suggests that miR-375 could be considered to be a key therapy target for OA. Differential expression analyses for mRNA and miRNA microarray datasets from ArrayExpress were performed. MiR-375 and ATG2B expressions in cartilage tissues were detected by qRT-PCR. Dual luciferase assay was applied to verify the targeting relationship between ATG2B and miR-375. , the role of miR-375 on chondrocyte autophagy and ERs was investigated by western blot and immunofluorescence. 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Dual luciferase assay was applied to verify the targeting relationship between ATG2B and miR-375. , the role of miR-375 on chondrocyte autophagy and ERs was investigated by western blot and immunofluorescence. The apoptotic rate was quantified by flow cytometry. , OA mice model was established, HE and Safranin O and Fast Green staining, as well as the OARSI and modified Mankin scores, were applied to measure the OA cartilage damage severity.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>32335541</pmid><doi>10.18632/aging.103073</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Apoptosis
Autophagy - genetics
Autophagy-Related Proteins - biosynthesis
Autophagy-Related Proteins - genetics
Cells, Cultured
Chondrocytes - metabolism
Chondrocytes - pathology
Disease Models, Animal
DNA Mutational Analysis
Gene Expression Regulation
Humans
Male
Mice
MicroRNAs - biosynthesis
MicroRNAs - genetics
Osteoarthritis, Knee - genetics
Osteoarthritis, Knee - metabolism
Osteoarthritis, Knee - pathology
Research Paper
RNA, Messenger - genetics
Signal Transduction
Vesicular Transport Proteins - biosynthesis
Vesicular Transport Proteins - genetics
title MicroRNA-375 exacerbates knee osteoarthritis through repressing chondrocyte autophagy by targeting ATG2B
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