Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases
Objectives To investigate the effect of leptin on cartilage destruction. Methods Collagen release was assessed in bovine cartilage explant cultures, while collagenolytic and gelatinolytic activities in culture supernatants were determined by bioassay and gelatin zymography. The expression of matrix...
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| Veröffentlicht in: | Annals of the rheumatic diseases 2012-03, Vol.71 (3), p.455-462 |
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| container_title | Annals of the rheumatic diseases |
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| creator | Hui, Wang Litherland, Gary J Elias, Martina S Kitson, Gareth I Cawston, Tim E Rowan, Andrew D Young, David A |
| description | Objectives To investigate the effect of leptin on cartilage destruction. Methods Collagen release was assessed in bovine cartilage explant cultures, while collagenolytic and gelatinolytic activities in culture supernatants were determined by bioassay and gelatin zymography. The expression of matrix metalloproteinases (MMP) was analysed by real-time RT–PCR. Signalling pathway activation was studied by immunoblotting. Leptin levels in cultured osteoarthritic joint infrapatellar fat pad or peri-enthesal deposit supernatants were measured by immunoassay. Results Leptin, either alone or in synergy with IL-1, significantly induced collagen release from bovine cartilage by upregulating collagenolytic and gelatinolytic activity. In chondrocytes, leptin induced MMP1 and MMP13 expression with a concomitant activation of STAT1, STAT3, STAT5, MAPK (JNK, Erk, p38), Akt and NF-κB signalling pathways. Selective inhibitor blockade of PI3K, p38, Erk and Akt pathways significantly reduced MMP1 and MMP13 expression in chondrocytes, and reduced cartilage collagen release induced by leptin or leptin plus IL-1. JNK inhibition had no effect on leptin-induced MMP13 expression or leptin plus IL-1-induced cartilage collagen release. Conditioned media from cultured white adipose tissue (WAT) from osteoarthritis knee joint fat pads contained leptin, induced cartilage collagen release and increased MMP1 and MMP13 expression in chondrocytes; the latter being partly blocked with an anti-leptin antibody. Conclusions Leptin acts as a pro-inflammatory adipokine with a catabolic role on cartilage metabolism via the upregulation of proteolytic enzymes and acts synergistically with other pro-inflammatory stimuli. This suggests that the infrapatellar fat pad and other WAT in arthritic joints are local producers of leptin, which may contribute to the inflammatory and degenerative processes in cartilage catabolism, providing a mechanistic link between obesity and osteoarthritis. |
| doi_str_mv | 10.1136/annrheumdis-2011-200372 |
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Methods Collagen release was assessed in bovine cartilage explant cultures, while collagenolytic and gelatinolytic activities in culture supernatants were determined by bioassay and gelatin zymography. The expression of matrix metalloproteinases (MMP) was analysed by real-time RT–PCR. Signalling pathway activation was studied by immunoblotting. Leptin levels in cultured osteoarthritic joint infrapatellar fat pad or peri-enthesal deposit supernatants were measured by immunoassay. Results Leptin, either alone or in synergy with IL-1, significantly induced collagen release from bovine cartilage by upregulating collagenolytic and gelatinolytic activity. In chondrocytes, leptin induced MMP1 and MMP13 expression with a concomitant activation of STAT1, STAT3, STAT5, MAPK (JNK, Erk, p38), Akt and NF-κB signalling pathways. Selective inhibitor blockade of PI3K, p38, Erk and Akt pathways significantly reduced MMP1 and MMP13 expression in chondrocytes, and reduced cartilage collagen release induced by leptin or leptin plus IL-1. JNK inhibition had no effect on leptin-induced MMP13 expression or leptin plus IL-1-induced cartilage collagen release. Conditioned media from cultured white adipose tissue (WAT) from osteoarthritis knee joint fat pads contained leptin, induced cartilage collagen release and increased MMP1 and MMP13 expression in chondrocytes; the latter being partly blocked with an anti-leptin antibody. Conclusions Leptin acts as a pro-inflammatory adipokine with a catabolic role on cartilage metabolism via the upregulation of proteolytic enzymes and acts synergistically with other pro-inflammatory stimuli. This suggests that the infrapatellar fat pad and other WAT in arthritic joints are local producers of leptin, which may contribute to the inflammatory and degenerative processes in cartilage catabolism, providing a mechanistic link between obesity and osteoarthritis.</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2011-200372</identifier><identifier>PMID: 22072016</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><subject>Adipose tissue ; Adipose Tissue, White - metabolism ; AKT protein ; Animals ; Arthritis ; Biological and medical sciences ; Body fat ; c-Jun amino-terminal kinase ; Cartilage diseases ; Cartilage, Articular - metabolism ; Cattle ; Cells, Cultured ; Chondrocytes ; Collagen ; Collagen - metabolism ; Collagenase 3 ; Collagenases - biosynthesis ; Collagenases - genetics ; Culture Media, Conditioned ; Cytokines ; Diseases of the osteoarticular system ; Dose-Response Relationship, Drug ; Enzymes ; Extracellular signal-regulated kinase ; Gene expression ; Gene Expression Regulation, Enzymologic - drug effects ; Growth factors ; Homeostasis ; Humans ; Immunoassays ; Inflammation ; Inflammation Mediators - pharmacology ; Interleukin 1 ; Joint diseases ; Leptin ; Leptin - biosynthesis ; Leptin - pharmacology ; Leptin - physiology ; MAP kinase ; Matrix metalloproteinase ; Matrix Metalloproteinases - metabolism ; Matrix Metalloproteinases - physiology ; Medical sciences ; Metabolism ; Mitogen-Activated Protein Kinase Kinases - metabolism ; Nasal Cartilages - drug effects ; Nasal Cartilages - metabolism ; Obesity ; Osteoarthritis ; Proto-Oncogene Proteins c-akt - metabolism ; Reverse Transcriptase Polymerase Chain Reaction - methods ; Rodents ; Signal transduction ; Signal Transduction - drug effects ; Signal Transduction - physiology ; STAT Transcription Factors - metabolism ; Stat1 protein ; Stat3 protein ; Tissue Culture Techniques</subject><ispartof>Annals of the rheumatic diseases, 2012-03, Vol.71 (3), p.455-462</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>2015 INIST-CNRS</rights><rights>Copyright: 2012 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b599t-4230b4d2dbd4a99d236dbb66ac2226529d986f5e5fc02b2eb60add28c6d536d63</citedby><cites>FETCH-LOGICAL-b599t-4230b4d2dbd4a99d236dbb66ac2226529d986f5e5fc02b2eb60add28c6d536d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/71/3/455.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/71/3/455.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,776,780,3183,23550,27901,27902,77342,77373</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26084254$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22072016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hui, Wang</creatorcontrib><creatorcontrib>Litherland, Gary J</creatorcontrib><creatorcontrib>Elias, Martina S</creatorcontrib><creatorcontrib>Kitson, Gareth I</creatorcontrib><creatorcontrib>Cawston, Tim E</creatorcontrib><creatorcontrib>Rowan, Andrew D</creatorcontrib><creatorcontrib>Young, David A</creatorcontrib><title>Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><description>Objectives To investigate the effect of leptin on cartilage destruction. Methods Collagen release was assessed in bovine cartilage explant cultures, while collagenolytic and gelatinolytic activities in culture supernatants were determined by bioassay and gelatin zymography. The expression of matrix metalloproteinases (MMP) was analysed by real-time RT–PCR. Signalling pathway activation was studied by immunoblotting. Leptin levels in cultured osteoarthritic joint infrapatellar fat pad or peri-enthesal deposit supernatants were measured by immunoassay. Results Leptin, either alone or in synergy with IL-1, significantly induced collagen release from bovine cartilage by upregulating collagenolytic and gelatinolytic activity. In chondrocytes, leptin induced MMP1 and MMP13 expression with a concomitant activation of STAT1, STAT3, STAT5, MAPK (JNK, Erk, p38), Akt and NF-κB signalling pathways. Selective inhibitor blockade of PI3K, p38, Erk and Akt pathways significantly reduced MMP1 and MMP13 expression in chondrocytes, and reduced cartilage collagen release induced by leptin or leptin plus IL-1. JNK inhibition had no effect on leptin-induced MMP13 expression or leptin plus IL-1-induced cartilage collagen release. Conditioned media from cultured white adipose tissue (WAT) from osteoarthritis knee joint fat pads contained leptin, induced cartilage collagen release and increased MMP1 and MMP13 expression in chondrocytes; the latter being partly blocked with an anti-leptin antibody. Conclusions Leptin acts as a pro-inflammatory adipokine with a catabolic role on cartilage metabolism via the upregulation of proteolytic enzymes and acts synergistically with other pro-inflammatory stimuli. This suggests that the infrapatellar fat pad and other WAT in arthritic joints are local producers of leptin, which may contribute to the inflammatory and degenerative processes in cartilage catabolism, providing a mechanistic link between obesity and osteoarthritis.</description><subject>Adipose tissue</subject><subject>Adipose Tissue, White - metabolism</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Biological and medical sciences</subject><subject>Body fat</subject><subject>c-Jun amino-terminal kinase</subject><subject>Cartilage diseases</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cattle</subject><subject>Cells, Cultured</subject><subject>Chondrocytes</subject><subject>Collagen</subject><subject>Collagen - metabolism</subject><subject>Collagenase 3</subject><subject>Collagenases - biosynthesis</subject><subject>Collagenases - genetics</subject><subject>Culture Media, Conditioned</subject><subject>Cytokines</subject><subject>Diseases of the osteoarticular system</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzymes</subject><subject>Extracellular signal-regulated kinase</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Growth factors</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Immunoassays</subject><subject>Inflammation</subject><subject>Inflammation Mediators - pharmacology</subject><subject>Interleukin 1</subject><subject>Joint diseases</subject><subject>Leptin</subject><subject>Leptin - biosynthesis</subject><subject>Leptin - pharmacology</subject><subject>Leptin - physiology</subject><subject>MAP kinase</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Matrix Metalloproteinases - physiology</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>Nasal Cartilages - drug effects</subject><subject>Nasal Cartilages - metabolism</subject><subject>Obesity</subject><subject>Osteoarthritis</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>STAT Transcription Factors - metabolism</subject><subject>Stat1 protein</subject><subject>Stat3 protein</subject><subject>Tissue Culture Techniques</subject><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkcFu1DAQhiMEotvCK4AlhOASsJ3ETo5oBS3SCoQElJs1sSdbL4mT2k5p34DHxqssK8QBcbH1j7_5x_afZU8ZfcVYIV6Dc_4K58HYkHPKWFpoIfm9bMVKUScl6P1sRVMxLxshT7LTEHZJ0prVD7MTzqlMbWKV_dzgFK0jkx_NrNGQ9o7sRusi-XFlIxIwdhoDkmhDmJFYt6cC0eCj7WGLxODWg4FoR0duLJB58rid-6UAzhDQ0d4scuzIANHbWzJghL4f09SI1kHA8Ch70EEf8PFhP8u-vHv7eX2Rbz6ev1-_2eRt1TQxL3lB29Jw05oSmsbwQpi2FQI051xUvDFNLboKq05T3nJsBQVjeK2FqRIqirPsxeKbZl_PGKIabNDY9-BwnINq0tfUDeN78uU_SUZ5TQtRcJrQZ3-hu3H2Lr1DMSllLRltqkTJhdJ-DMFjpyZvB_B3yUrtY1V_xKr2saol1tT55OA_twOaY9_vHBPw_ABA0NB3HpxOHkdO0LrkVZm4fOFsiHh7PAf_XQlZyEp9-LpWFb8sxOX5J_Ut8Xzh22H337f9BRZh0K0</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Hui, Wang</creator><creator>Litherland, Gary J</creator><creator>Elias, Martina S</creator><creator>Kitson, Gareth I</creator><creator>Cawston, Tim E</creator><creator>Rowan, Andrew D</creator><creator>Young, David A</creator><general>BMJ Publishing Group Ltd and European League Against Rheumatism</general><general>BMJ Publishing Group</general><general>Elsevier Limited</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7QP</scope><scope>7X8</scope></search><sort><creationdate>20120301</creationdate><title>Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases</title><author>Hui, Wang ; Litherland, Gary J ; Elias, Martina S ; Kitson, Gareth I ; Cawston, Tim E ; Rowan, Andrew D ; Young, David A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b599t-4230b4d2dbd4a99d236dbb66ac2226529d986f5e5fc02b2eb60add28c6d536d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue, White - metabolism</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Arthritis</topic><topic>Biological and medical sciences</topic><topic>Body fat</topic><topic>c-Jun amino-terminal kinase</topic><topic>Cartilage diseases</topic><topic>Cartilage, Articular - metabolism</topic><topic>Cattle</topic><topic>Cells, Cultured</topic><topic>Chondrocytes</topic><topic>Collagen</topic><topic>Collagen - metabolism</topic><topic>Collagenase 3</topic><topic>Collagenases - biosynthesis</topic><topic>Collagenases - genetics</topic><topic>Culture Media, Conditioned</topic><topic>Cytokines</topic><topic>Diseases of the osteoarticular system</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzymes</topic><topic>Extracellular signal-regulated kinase</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Growth factors</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Immunoassays</topic><topic>Inflammation</topic><topic>Inflammation Mediators - pharmacology</topic><topic>Interleukin 1</topic><topic>Joint diseases</topic><topic>Leptin</topic><topic>Leptin - biosynthesis</topic><topic>Leptin - pharmacology</topic><topic>Leptin - physiology</topic><topic>MAP kinase</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinases - metabolism</topic><topic>Matrix Metalloproteinases - physiology</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Mitogen-Activated Protein Kinase Kinases - metabolism</topic><topic>Nasal Cartilages - drug effects</topic><topic>Nasal Cartilages - metabolism</topic><topic>Obesity</topic><topic>Osteoarthritis</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - methods</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>STAT Transcription Factors - metabolism</topic><topic>Stat1 protein</topic><topic>Stat3 protein</topic><topic>Tissue Culture Techniques</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hui, Wang</creatorcontrib><creatorcontrib>Litherland, Gary J</creatorcontrib><creatorcontrib>Elias, Martina S</creatorcontrib><creatorcontrib>Kitson, Gareth I</creatorcontrib><creatorcontrib>Cawston, Tim E</creatorcontrib><creatorcontrib>Rowan, Andrew D</creatorcontrib><creatorcontrib>Young, David A</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hui, Wang</au><au>Litherland, Gary J</au><au>Elias, Martina S</au><au>Kitson, Gareth I</au><au>Cawston, Tim E</au><au>Rowan, Andrew D</au><au>Young, David A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases</atitle><jtitle>Annals of the rheumatic diseases</jtitle><addtitle>Ann Rheum Dis</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>71</volume><issue>3</issue><spage>455</spage><epage>462</epage><pages>455-462</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>Objectives To investigate the effect of leptin on cartilage destruction. Methods Collagen release was assessed in bovine cartilage explant cultures, while collagenolytic and gelatinolytic activities in culture supernatants were determined by bioassay and gelatin zymography. The expression of matrix metalloproteinases (MMP) was analysed by real-time RT–PCR. Signalling pathway activation was studied by immunoblotting. Leptin levels in cultured osteoarthritic joint infrapatellar fat pad or peri-enthesal deposit supernatants were measured by immunoassay. Results Leptin, either alone or in synergy with IL-1, significantly induced collagen release from bovine cartilage by upregulating collagenolytic and gelatinolytic activity. In chondrocytes, leptin induced MMP1 and MMP13 expression with a concomitant activation of STAT1, STAT3, STAT5, MAPK (JNK, Erk, p38), Akt and NF-κB signalling pathways. Selective inhibitor blockade of PI3K, p38, Erk and Akt pathways significantly reduced MMP1 and MMP13 expression in chondrocytes, and reduced cartilage collagen release induced by leptin or leptin plus IL-1. JNK inhibition had no effect on leptin-induced MMP13 expression or leptin plus IL-1-induced cartilage collagen release. Conditioned media from cultured white adipose tissue (WAT) from osteoarthritis knee joint fat pads contained leptin, induced cartilage collagen release and increased MMP1 and MMP13 expression in chondrocytes; the latter being partly blocked with an anti-leptin antibody. Conclusions Leptin acts as a pro-inflammatory adipokine with a catabolic role on cartilage metabolism via the upregulation of proteolytic enzymes and acts synergistically with other pro-inflammatory stimuli. This suggests that the infrapatellar fat pad and other WAT in arthritic joints are local producers of leptin, which may contribute to the inflammatory and degenerative processes in cartilage catabolism, providing a mechanistic link between obesity and osteoarthritis.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and European League Against Rheumatism</pub><pmid>22072016</pmid><doi>10.1136/annrheumdis-2011-200372</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipose tissue Adipose Tissue, White - metabolism AKT protein Animals Arthritis Biological and medical sciences Body fat c-Jun amino-terminal kinase Cartilage diseases Cartilage, Articular - metabolism Cattle Cells, Cultured Chondrocytes Collagen Collagen - metabolism Collagenase 3 Collagenases - biosynthesis Collagenases - genetics Culture Media, Conditioned Cytokines Diseases of the osteoarticular system Dose-Response Relationship, Drug Enzymes Extracellular signal-regulated kinase Gene expression Gene Expression Regulation, Enzymologic - drug effects Growth factors Homeostasis Humans Immunoassays Inflammation Inflammation Mediators - pharmacology Interleukin 1 Joint diseases Leptin Leptin - biosynthesis Leptin - pharmacology Leptin - physiology MAP kinase Matrix metalloproteinase Matrix Metalloproteinases - metabolism Matrix Metalloproteinases - physiology Medical sciences Metabolism Mitogen-Activated Protein Kinase Kinases - metabolism Nasal Cartilages - drug effects Nasal Cartilages - metabolism Obesity Osteoarthritis Proto-Oncogene Proteins c-akt - metabolism Reverse Transcriptase Polymerase Chain Reaction - methods Rodents Signal transduction Signal Transduction - drug effects Signal Transduction - physiology STAT Transcription Factors - metabolism Stat1 protein Stat3 protein Tissue Culture Techniques |
| title | Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases |
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