Sucrose, But Not Glucose, Blocks IL1‐β‐Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway

ABSTRACT Pathogenesis of osteoarthritis (OA) is multifactorial but interleukin‐1β (IL‐1β) is known to be an important mediator of cartilage degradation. Autophagy is an essential cellular homeostasis mechanism and has been proposed to protect against cartilage degradation and chondrocyte death under...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of cellular biochemistry 2017-03, Vol.118 (3), p.629-639
Hauptverfasser: Khan, Nazir M., Ansari, Mohammad Y., Haqqi, Tariq M.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 639
container_issue 3
container_start_page 629
container_title Journal of cellular biochemistry
container_volume 118
creator Khan, Nazir M.
Ansari, Mohammad Y.
Haqqi, Tariq M.
description ABSTRACT Pathogenesis of osteoarthritis (OA) is multifactorial but interleukin‐1β (IL‐1β) is known to be an important mediator of cartilage degradation. Autophagy is an essential cellular homeostasis mechanism and has been proposed to protect against cartilage degradation and chondrocyte death under pathological conditions. We investigated the role of autophagy activated by sucrose, a natural disaccharide, in suppressing inflammatory mediator's expression and cell death under pathological conditions in human chondrocytes. Autophagy activation was investigated by Western blotting for LC3 and Beclin‐1, immunofluorescence staining for LC3 puncta, and measuring autophagic flux. Activation of mTOR, AKT, and P70S6K was evaluated by Western blotting. Chondrocyte apoptosis was evaluated by propidium iodide (PI) staining using flowcytometry, expression of Bax by Western blotting, gene expression by TaqMan assays and caspase 3/7 activity was measured using a luminescence‐based assay. We found that sucrose‐induced active autophagy in OA chondrocytes in vitro was dependent on the activation of AKT/mTOR/P70S6K signaling pathways but was independent of reactive oxygen species (ROS) production. Sucrose activated autophagy blocked IL‐1β‐induced apoptosis and mRNA expression of MMP‐13, COX‐2, and IL‐6 in human OA chondrocytes. Glucose or fructose, the two metabolites of sucrose, failed to induce autophagy indicating that autophagy was specifically mediated by sucrose. In conclusion, sucrose attenuated IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes. J. Cell. Biochem. 118: 629–639, 2017. © 2016 Wiley Periodicals, Inc. Our data demonstrate that sucrose attenuate IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes.
doi_str_mv 10.1002/jcb.25750
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5490987</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1835418108</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2960-6d8fef7484dcd776390079e284488e7ec613839d43293cd8b21c60a3160415d13</originalsourceid><addsrcrecordid>eNpVUctuEzEUtRAVDYUFP4C8ZME0fo0fG6Q0gjZtRFEJa8uxnWTKjJ2Ox61mx5oV38KH8BF8SYekVLC59-qec8-R7gHgFUbHGCEyvrbLY1KKEj0BI4yUKBhn7CkYIUFRQSgmh-B5StcIIaUoeQYOieBclQyPwPfP2bYx-bfwJHfwY-zgaZ3tflFH-zXB2Rz__vbj18-hzILL1js4C6vaNI3pYtvDK5-2MSQPqwDPcmMCnG5icG20fecTXPZwd1aFNZzkLm43Zt3D28rAycVi3Cwur-An023uTP8CHKxMnfzLh34Evnx4v5ieFfPL09l0Mi8sURwV3MmVXwkmmbNOCE4VQkJ5IhmT0gtvOaaSKscoUdQ6uSTYcmQo5ojh0mF6BN7tdbd52XhnfehaU-ttWzWm7XU0lf4fCdVGr-OtLplCSopB4M2DQBtvsk-dbqpkfV2b4GNOGks6_FZiJAfq63-9Hk3-BjAQxnvCXVX7_hHHSP9JVg_J6l2y-nx6shvoPdRLmJs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1835418108</pqid></control><display><type>article</type><title>Sucrose, But Not Glucose, Blocks IL1‐β‐Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Khan, Nazir M. ; Ansari, Mohammad Y. ; Haqqi, Tariq M.</creator><creatorcontrib>Khan, Nazir M. ; Ansari, Mohammad Y. ; Haqqi, Tariq M.</creatorcontrib><description>ABSTRACT Pathogenesis of osteoarthritis (OA) is multifactorial but interleukin‐1β (IL‐1β) is known to be an important mediator of cartilage degradation. Autophagy is an essential cellular homeostasis mechanism and has been proposed to protect against cartilage degradation and chondrocyte death under pathological conditions. We investigated the role of autophagy activated by sucrose, a natural disaccharide, in suppressing inflammatory mediator's expression and cell death under pathological conditions in human chondrocytes. Autophagy activation was investigated by Western blotting for LC3 and Beclin‐1, immunofluorescence staining for LC3 puncta, and measuring autophagic flux. Activation of mTOR, AKT, and P70S6K was evaluated by Western blotting. Chondrocyte apoptosis was evaluated by propidium iodide (PI) staining using flowcytometry, expression of Bax by Western blotting, gene expression by TaqMan assays and caspase 3/7 activity was measured using a luminescence‐based assay. We found that sucrose‐induced active autophagy in OA chondrocytes in vitro was dependent on the activation of AKT/mTOR/P70S6K signaling pathways but was independent of reactive oxygen species (ROS) production. Sucrose activated autophagy blocked IL‐1β‐induced apoptosis and mRNA expression of MMP‐13, COX‐2, and IL‐6 in human OA chondrocytes. Glucose or fructose, the two metabolites of sucrose, failed to induce autophagy indicating that autophagy was specifically mediated by sucrose. In conclusion, sucrose attenuated IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes. J. Cell. Biochem. 118: 629–639, 2017. © 2016 Wiley Periodicals, Inc. Our data demonstrate that sucrose attenuate IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.25750</identifier><identifier>PMID: 27669541</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; AUTOPHAGY ; Autophagy - drug effects ; CHONDROCYTES ; Chondrocytes - metabolism ; Chondrocytes - pathology ; Female ; Glucose - pharmacology ; Humans ; Inflammation - chemically induced ; Inflammation - metabolism ; Inflammation - pathology ; Interleukin-1beta - pharmacology ; Male ; Middle Aged ; OSTEOARTHRITIS ; Osteoarthritis - metabolism ; Osteoarthritis - pathology ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction - drug effects ; SUCROSE ; Sucrose - pharmacology ; TOR Serine-Threonine Kinases - metabolism</subject><ispartof>Journal of cellular biochemistry, 2017-03, Vol.118 (3), p.629-639</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2960-6d8fef7484dcd776390079e284488e7ec613839d43293cd8b21c60a3160415d13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.25750$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.25750$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27669541$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, Nazir M.</creatorcontrib><creatorcontrib>Ansari, Mohammad Y.</creatorcontrib><creatorcontrib>Haqqi, Tariq M.</creatorcontrib><title>Sucrose, But Not Glucose, Blocks IL1‐β‐Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway</title><title>Journal of cellular biochemistry</title><addtitle>J Cell Biochem</addtitle><description>ABSTRACT Pathogenesis of osteoarthritis (OA) is multifactorial but interleukin‐1β (IL‐1β) is known to be an important mediator of cartilage degradation. Autophagy is an essential cellular homeostasis mechanism and has been proposed to protect against cartilage degradation and chondrocyte death under pathological conditions. We investigated the role of autophagy activated by sucrose, a natural disaccharide, in suppressing inflammatory mediator's expression and cell death under pathological conditions in human chondrocytes. Autophagy activation was investigated by Western blotting for LC3 and Beclin‐1, immunofluorescence staining for LC3 puncta, and measuring autophagic flux. Activation of mTOR, AKT, and P70S6K was evaluated by Western blotting. Chondrocyte apoptosis was evaluated by propidium iodide (PI) staining using flowcytometry, expression of Bax by Western blotting, gene expression by TaqMan assays and caspase 3/7 activity was measured using a luminescence‐based assay. We found that sucrose‐induced active autophagy in OA chondrocytes in vitro was dependent on the activation of AKT/mTOR/P70S6K signaling pathways but was independent of reactive oxygen species (ROS) production. Sucrose activated autophagy blocked IL‐1β‐induced apoptosis and mRNA expression of MMP‐13, COX‐2, and IL‐6 in human OA chondrocytes. Glucose or fructose, the two metabolites of sucrose, failed to induce autophagy indicating that autophagy was specifically mediated by sucrose. In conclusion, sucrose attenuated IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes. J. Cell. Biochem. 118: 629–639, 2017. © 2016 Wiley Periodicals, Inc. Our data demonstrate that sucrose attenuate IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes.</description><subject>Adult</subject><subject>Aged</subject><subject>AUTOPHAGY</subject><subject>Autophagy - drug effects</subject><subject>CHONDROCYTES</subject><subject>Chondrocytes - metabolism</subject><subject>Chondrocytes - pathology</subject><subject>Female</subject><subject>Glucose - pharmacology</subject><subject>Humans</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>OSTEOARTHRITIS</subject><subject>Osteoarthritis - metabolism</subject><subject>Osteoarthritis - pathology</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>SUCROSE</subject><subject>Sucrose - pharmacology</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctuEzEUtRAVDYUFP4C8ZME0fo0fG6Q0gjZtRFEJa8uxnWTKjJ2Ox61mx5oV38KH8BF8SYekVLC59-qec8-R7gHgFUbHGCEyvrbLY1KKEj0BI4yUKBhn7CkYIUFRQSgmh-B5StcIIaUoeQYOieBclQyPwPfP2bYx-bfwJHfwY-zgaZ3tflFH-zXB2Rz__vbj18-hzILL1js4C6vaNI3pYtvDK5-2MSQPqwDPcmMCnG5icG20fecTXPZwd1aFNZzkLm43Zt3D28rAycVi3Cwur-An023uTP8CHKxMnfzLh34Evnx4v5ieFfPL09l0Mi8sURwV3MmVXwkmmbNOCE4VQkJ5IhmT0gtvOaaSKscoUdQ6uSTYcmQo5ojh0mF6BN7tdbd52XhnfehaU-ttWzWm7XU0lf4fCdVGr-OtLplCSopB4M2DQBtvsk-dbqpkfV2b4GNOGks6_FZiJAfq63-9Hk3-BjAQxnvCXVX7_hHHSP9JVg_J6l2y-nx6shvoPdRLmJs</recordid><startdate>201703</startdate><enddate>201703</enddate><creator>Khan, Nazir M.</creator><creator>Ansari, Mohammad Y.</creator><creator>Haqqi, Tariq M.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201703</creationdate><title>Sucrose, But Not Glucose, Blocks IL1‐β‐Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway</title><author>Khan, Nazir M. ; Ansari, Mohammad Y. ; Haqqi, Tariq M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2960-6d8fef7484dcd776390079e284488e7ec613839d43293cd8b21c60a3160415d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>AUTOPHAGY</topic><topic>Autophagy - drug effects</topic><topic>CHONDROCYTES</topic><topic>Chondrocytes - metabolism</topic><topic>Chondrocytes - pathology</topic><topic>Female</topic><topic>Glucose - pharmacology</topic><topic>Humans</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>OSTEOARTHRITIS</topic><topic>Osteoarthritis - metabolism</topic><topic>Osteoarthritis - pathology</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>SUCROSE</topic><topic>Sucrose - pharmacology</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khan, Nazir M.</creatorcontrib><creatorcontrib>Ansari, Mohammad Y.</creatorcontrib><creatorcontrib>Haqqi, Tariq M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, Nazir M.</au><au>Ansari, Mohammad Y.</au><au>Haqqi, Tariq M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sucrose, But Not Glucose, Blocks IL1‐β‐Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J Cell Biochem</addtitle><date>2017-03</date><risdate>2017</risdate><volume>118</volume><issue>3</issue><spage>629</spage><epage>639</epage><pages>629-639</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>ABSTRACT Pathogenesis of osteoarthritis (OA) is multifactorial but interleukin‐1β (IL‐1β) is known to be an important mediator of cartilage degradation. Autophagy is an essential cellular homeostasis mechanism and has been proposed to protect against cartilage degradation and chondrocyte death under pathological conditions. We investigated the role of autophagy activated by sucrose, a natural disaccharide, in suppressing inflammatory mediator's expression and cell death under pathological conditions in human chondrocytes. Autophagy activation was investigated by Western blotting for LC3 and Beclin‐1, immunofluorescence staining for LC3 puncta, and measuring autophagic flux. Activation of mTOR, AKT, and P70S6K was evaluated by Western blotting. Chondrocyte apoptosis was evaluated by propidium iodide (PI) staining using flowcytometry, expression of Bax by Western blotting, gene expression by TaqMan assays and caspase 3/7 activity was measured using a luminescence‐based assay. We found that sucrose‐induced active autophagy in OA chondrocytes in vitro was dependent on the activation of AKT/mTOR/P70S6K signaling pathways but was independent of reactive oxygen species (ROS) production. Sucrose activated autophagy blocked IL‐1β‐induced apoptosis and mRNA expression of MMP‐13, COX‐2, and IL‐6 in human OA chondrocytes. Glucose or fructose, the two metabolites of sucrose, failed to induce autophagy indicating that autophagy was specifically mediated by sucrose. In conclusion, sucrose attenuated IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes. J. Cell. Biochem. 118: 629–639, 2017. © 2016 Wiley Periodicals, Inc. Our data demonstrate that sucrose attenuate IL‐1β induced apoptosis and the expression of catabolic mediators by inducing autophagy, and the autophagy in part was mediated through the activation of AKT/mTOR/P70S6K signaling pathway in human OA chondrocytes.</abstract><cop>United States</cop><pmid>27669541</pmid><doi>10.1002/jcb.25750</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0730-2312
ispartof Journal of cellular biochemistry, 2017-03, Vol.118 (3), p.629-639
issn 0730-2312
1097-4644
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5490987
source MEDLINE; Access via Wiley Online Library
subjects Adult
Aged
AUTOPHAGY
Autophagy - drug effects
CHONDROCYTES
Chondrocytes - metabolism
Chondrocytes - pathology
Female
Glucose - pharmacology
Humans
Inflammation - chemically induced
Inflammation - metabolism
Inflammation - pathology
Interleukin-1beta - pharmacology
Male
Middle Aged
OSTEOARTHRITIS
Osteoarthritis - metabolism
Osteoarthritis - pathology
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction - drug effects
SUCROSE
Sucrose - pharmacology
TOR Serine-Threonine Kinases - metabolism
title Sucrose, But Not Glucose, Blocks IL1‐β‐Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T17%3A03%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sucrose,%20But%20Not%20Glucose,%20Blocks%20IL1%E2%80%90%CE%B2%E2%80%90Induced%20Inflammatory%20Response%20in%20Human%20Chondrocytes%20by%20Inducing%20Autophagy%20via%20AKT/mTOR%20Pathway&rft.jtitle=Journal%20of%20cellular%20biochemistry&rft.au=Khan,%20Nazir%20M.&rft.date=2017-03&rft.volume=118&rft.issue=3&rft.spage=629&rft.epage=639&rft.pages=629-639&rft.issn=0730-2312&rft.eissn=1097-4644&rft_id=info:doi/10.1002/jcb.25750&rft_dat=%3Cproquest_pubme%3E1835418108%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1835418108&rft_id=info:pmid/27669541&rfr_iscdi=true