IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells
Mesenchymal stem cells (MSCs) can differentiate into cells of mesenchymal lineages, such as osteoblasts and chondrocytes. Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs. Human bone marrow MSCs were pellet cultured in c...
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| Veröffentlicht in: | PloS one 2013-11, Vol.8 (11), p.e79463 |
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| creator | Kondo, Masahiro Yamaoka, Kunihiro Sonomoto, Koshiro Fukuyo, Shunsuke Oshita, Koichi Okada, Yosuke Tanaka, Yoshiya |
| description | Mesenchymal stem cells (MSCs) can differentiate into cells of mesenchymal lineages, such as osteoblasts and chondrocytes. Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs.
Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression.
Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA), which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis.
IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation. |
| doi_str_mv | 10.1371/journal.pone.0079463 |
| format | Article |
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Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression.
Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA), which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis.
IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0079463</identifier><identifier>PMID: 24260226</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biocompatibility ; Biomedical materials ; Bone marrow ; Bone morphogenetic proteins ; Cartilage ; Cell Differentiation - drug effects ; Cells, Cultured ; Chondrocytes ; Chondrogenesis ; Chondrogenesis - drug effects ; Cyclic adenosine monophosphate ; Cytokines ; Differentiation ; Environmental health ; Gene expression ; Genes ; Growth factors ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin 17 ; Interleukin-17 - pharmacology ; Internal medicine ; Kinases ; Laboratories ; Medicine ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Mesenchyme ; Metabolism ; Microscopy, Fluorescence ; Osteoblasts ; Overexpression ; Phosphorylation ; Phosphorylation - drug effects ; Protein kinase A ; Protein kinases ; Proteins ; Rheumatoid arthritis ; Rodents ; Sox9 protein ; SOX9 Transcription Factor - metabolism ; Stem cells ; Transforming growth factors</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e79463</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Kondo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Kondo et al 2013 Kondo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-24534659618343cebe4ca00f31685c70a24bea5344b31603d679e6cd80c985043</citedby><cites>FETCH-LOGICAL-c692t-24534659618343cebe4ca00f31685c70a24bea5344b31603d679e6cd80c985043</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/PMC3829852/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829852/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24260226$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Barbosa, Mário A.</contributor><creatorcontrib>Kondo, Masahiro</creatorcontrib><creatorcontrib>Yamaoka, Kunihiro</creatorcontrib><creatorcontrib>Sonomoto, Koshiro</creatorcontrib><creatorcontrib>Fukuyo, Shunsuke</creatorcontrib><creatorcontrib>Oshita, Koichi</creatorcontrib><creatorcontrib>Okada, Yosuke</creatorcontrib><creatorcontrib>Tanaka, Yoshiya</creatorcontrib><title>IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mesenchymal stem cells (MSCs) can differentiate into cells of mesenchymal lineages, such as osteoblasts and chondrocytes. Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs.
Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression.
Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA), which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis.
IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation.</description><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Bone marrow</subject><subject>Bone morphogenetic proteins</subject><subject>Cartilage</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Chondrocytes</subject><subject>Chondrogenesis</subject><subject>Chondrogenesis - drug effects</subject><subject>Cyclic adenosine monophosphate</subject><subject>Cytokines</subject><subject>Differentiation</subject><subject>Environmental health</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Interleukin 17</subject><subject>Interleukin-17 - pharmacology</subject><subject>Internal medicine</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Medicine</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Mesenchyme</subject><subject>Metabolism</subject><subject>Microscopy, Fluorescence</subject><subject>Osteoblasts</subject><subject>Overexpression</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Protein kinase A</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Rheumatoid arthritis</subject><subject>Rodents</subject><subject>Sox9 protein</subject><subject>SOX9 Transcription Factor - metabolism</subject><subject>Stem cells</subject><subject>Transforming growth factors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLguBFx3y3uRGWxY_BgQW_bkOank4ztMls0or778043WUKCpKLhJPnvOfw8mbZc4xWmJb47c5Pwel-tfcOVgiVkgn6IDvHkpJCEEQfnrzPsicx7hDitBLicXZGGBGIEHGefV5vClzm1nW2tmPMTeddE_wWnDV5Y9sWArjR6tF6l_s276ZBu3yACM50t4Pu8zjCkBvo-_g0e9TqPsKz-b7Ivn94_-3qU7G5_ri-utwURkgyFoRxygSXAleUUQM1MKMRaikWFTcl0oTVoBPD6lRCtBGlBGGaChlZccToRfbyqLvvfVSzD1FhxquScc5FItZHovF6p_bBDjrcKq-t-lPwYat0GK3pQWkkeSWlxEzgNJHLsmWl1AIIaxuoq6T1bp421QM0JtkRdL8QXf4426mt_6loRdK-JAm8mgWCv5kgjv9Yeaa2Om1lXeuTmBlsNOqSlRURpEQ0Uau_UOk0MFiTktDaVF80vFk0JGaEX-NWTzGq9dcv_89e_1iyr0_YDnQ_dtH30yEncQmyI2iCjzFAe-8cRuoQ5Ds31CHIag5yantx6vp9011y6W-J1uuj</recordid><startdate>20131115</startdate><enddate>20131115</enddate><creator>Kondo, Masahiro</creator><creator>Yamaoka, Kunihiro</creator><creator>Sonomoto, Koshiro</creator><creator>Fukuyo, Shunsuke</creator><creator>Oshita, Koichi</creator><creator>Okada, Yosuke</creator><creator>Tanaka, Yoshiya</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131115</creationdate><title>IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells</title><author>Kondo, Masahiro ; Yamaoka, Kunihiro ; Sonomoto, Koshiro ; Fukuyo, Shunsuke ; Oshita, Koichi ; Okada, Yosuke ; Tanaka, Yoshiya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-24534659618343cebe4ca00f31685c70a24bea5344b31603d679e6cd80c985043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Bone marrow</topic><topic>Bone morphogenetic proteins</topic><topic>Cartilage</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Chondrocytes</topic><topic>Chondrogenesis</topic><topic>Chondrogenesis - drug effects</topic><topic>Cyclic adenosine monophosphate</topic><topic>Cytokines</topic><topic>Differentiation</topic><topic>Environmental health</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Interleukin 17</topic><topic>Interleukin-17 - pharmacology</topic><topic>Internal medicine</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Medicine</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Mesenchyme</topic><topic>Metabolism</topic><topic>Microscopy, Fluorescence</topic><topic>Osteoblasts</topic><topic>Overexpression</topic><topic>Phosphorylation</topic><topic>Phosphorylation - drug effects</topic><topic>Protein kinase A</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Rheumatoid arthritis</topic><topic>Rodents</topic><topic>Sox9 protein</topic><topic>SOX9 Transcription Factor - 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Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs.
Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression.
Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA), which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis.
IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24260226</pmid><doi>10.1371/journal.pone.0079463</doi><tpages>e79463</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biocompatibility Biomedical materials Bone marrow Bone morphogenetic proteins Cartilage Cell Differentiation - drug effects Cells, Cultured Chondrocytes Chondrogenesis Chondrogenesis - drug effects Cyclic adenosine monophosphate Cytokines Differentiation Environmental health Gene expression Genes Growth factors Humans Immunohistochemistry Inflammation Interleukin 17 Interleukin-17 - pharmacology Internal medicine Kinases Laboratories Medicine Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mesenchyme Metabolism Microscopy, Fluorescence Osteoblasts Overexpression Phosphorylation Phosphorylation - drug effects Protein kinase A Protein kinases Proteins Rheumatoid arthritis Rodents Sox9 protein SOX9 Transcription Factor - metabolism Stem cells Transforming growth factors |
| title | IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells |
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