Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis
Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43...
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| Veröffentlicht in: | Aging (Albany, NY.) NY.), 2020-08, Vol.12 (16), p.15882-15905 |
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| creator | Varela-Eirín, Marta Carpintero-Fernández, Paula Sánchez-Temprano, Agustín Varela-Vázquez, Adrián Paíno, Carlos Luis Casado-Díaz, Antonio Continente, Alfonso Calañas Mato, Virginia Fonseca, Eduardo Kandouz, Mustapha Blanco, Alfonso Caeiro, José Ramón Mayán, María D |
| description | Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our
results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease. |
| doi_str_mv | 10.18632/aging.103801 |
| format | Article |
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results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease.</description><identifier>ISSN: 1945-4589</identifier><identifier>EISSN: 1945-4589</identifier><identifier>DOI: 10.18632/aging.103801</identifier><identifier>PMID: 32745074</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>Aged ; Antirheumatic Agents - isolation & purification ; Antirheumatic Agents - pharmacology ; Cartilage, Articular - drug effects ; Cartilage, Articular - metabolism ; Cartilage, Articular - pathology ; Cell Differentiation - drug effects ; Cell Line ; Cellular Microenvironment ; Cellular Senescence - drug effects ; Chondrocytes - drug effects ; Chondrocytes - metabolism ; Chondrocytes - pathology ; Chondrogenesis - drug effects ; Collagen Type II - metabolism ; Connexin 43 - genetics ; Connexin 43 - metabolism ; Female ; Fruit ; Humans ; Iridoids - isolation & purification ; Iridoids - pharmacology ; Male ; NF-kappa B - metabolism ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Olea - chemistry ; Osteoarthritis - drug therapy ; Osteoarthritis - genetics ; Osteoarthritis - metabolism ; Osteoarthritis - pathology ; Osteogenesis - drug effects ; Polyphenols - isolation & purification ; Polyphenols - pharmacology ; Priority Research Paper ; Regeneration - drug effects ; Signal Transduction ; Twist-Related Protein 1 - genetics ; Twist-Related Protein 1 - metabolism</subject><ispartof>Aging (Albany, NY.), 2020-08, Vol.12 (16), p.15882-15905</ispartof><rights>Copyright © 2020 Varela-Eirín et al.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-355543aea57cbf083aa5a8fa166617f12178d752d8da50d0303e52cd1c25a92e3</citedby><cites>FETCH-LOGICAL-c387t-355543aea57cbf083aa5a8fa166617f12178d752d8da50d0303e52cd1c25a92e3</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/PMC7485729/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485729/$$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/32745074$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Varela-Eirín, Marta</creatorcontrib><creatorcontrib>Carpintero-Fernández, Paula</creatorcontrib><creatorcontrib>Sánchez-Temprano, Agustín</creatorcontrib><creatorcontrib>Varela-Vázquez, Adrián</creatorcontrib><creatorcontrib>Paíno, Carlos Luis</creatorcontrib><creatorcontrib>Casado-Díaz, Antonio</creatorcontrib><creatorcontrib>Continente, Alfonso Calañas</creatorcontrib><creatorcontrib>Mato, Virginia</creatorcontrib><creatorcontrib>Fonseca, Eduardo</creatorcontrib><creatorcontrib>Kandouz, Mustapha</creatorcontrib><creatorcontrib>Blanco, Alfonso</creatorcontrib><creatorcontrib>Caeiro, José Ramón</creatorcontrib><creatorcontrib>Mayán, María D</creatorcontrib><title>Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis</title><title>Aging (Albany, NY.)</title><addtitle>Aging (Albany NY)</addtitle><description>Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our
results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease.</description><subject>Aged</subject><subject>Antirheumatic Agents - isolation & purification</subject><subject>Antirheumatic Agents - pharmacology</subject><subject>Cartilage, Articular - drug effects</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cartilage, Articular - pathology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line</subject><subject>Cellular Microenvironment</subject><subject>Cellular Senescence - drug effects</subject><subject>Chondrocytes - drug effects</subject><subject>Chondrocytes - metabolism</subject><subject>Chondrocytes - pathology</subject><subject>Chondrogenesis - drug effects</subject><subject>Collagen Type II - metabolism</subject><subject>Connexin 43 - genetics</subject><subject>Connexin 43 - metabolism</subject><subject>Female</subject><subject>Fruit</subject><subject>Humans</subject><subject>Iridoids - isolation & purification</subject><subject>Iridoids - pharmacology</subject><subject>Male</subject><subject>NF-kappa B - metabolism</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Olea - chemistry</subject><subject>Osteoarthritis - drug therapy</subject><subject>Osteoarthritis - genetics</subject><subject>Osteoarthritis - metabolism</subject><subject>Osteoarthritis - pathology</subject><subject>Osteogenesis - drug effects</subject><subject>Polyphenols - isolation & purification</subject><subject>Polyphenols - pharmacology</subject><subject>Priority Research Paper</subject><subject>Regeneration - drug effects</subject><subject>Signal Transduction</subject><subject>Twist-Related Protein 1 - genetics</subject><subject>Twist-Related Protein 1 - metabolism</subject><issn>1945-4589</issn><issn>1945-4589</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1vFDEMhiMEoqVw5Ipy5DIlH5PJzAUJVXxUqsQBOEdu4tkNyiRDkl1pf07_KdluqcolsezHr528hLzl7JKPgxQfYOPj5pIzOTL-jJzzqVddr8bp-ZP4jLwq5Tdjg1L98JKcSaF7xXR_Tu5-YEzhUL2lYKvf-3qgaaZlgRDokgLaXYBM18as2yNa6JzTQlPwe6QZS03toHabosvJHuox6fw8Y8ZYPVSfIoXo6Nq6Um0oHMMu4wYj5lZvMhj3Pqe4tA7qI02lYoJct9lXX16TFzOEgm8e7gvy68vnn1ffupvvX6-vPt10Vo66dlK1t0lAUNrezmyUAArGGfgwDFzPXHA9Oq2EGx0o5phkEpWwjluhYBIoL8jHk-66u13Q2bZMhmDW7BfIB5PAm_8r0W_NJu2N7kelxdQE3j8I5PRn137GLL5YDAEipl0xom8zNR8m1tDuhNqcSsk4P47hzNzbau5tNSdbG__u6W6P9D8f5V-N-aYr</recordid><startdate>20200803</startdate><enddate>20200803</enddate><creator>Varela-Eirín, Marta</creator><creator>Carpintero-Fernández, Paula</creator><creator>Sánchez-Temprano, Agustín</creator><creator>Varela-Vázquez, Adrián</creator><creator>Paíno, Carlos Luis</creator><creator>Casado-Díaz, Antonio</creator><creator>Continente, Alfonso Calañas</creator><creator>Mato, Virginia</creator><creator>Fonseca, Eduardo</creator><creator>Kandouz, Mustapha</creator><creator>Blanco, Alfonso</creator><creator>Caeiro, José Ramón</creator><creator>Mayán, María D</creator><general>Impact Journals</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200803</creationdate><title>Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis</title><author>Varela-Eirín, Marta ; Carpintero-Fernández, Paula ; Sánchez-Temprano, Agustín ; Varela-Vázquez, Adrián ; Paíno, Carlos Luis ; Casado-Díaz, Antonio ; Continente, Alfonso Calañas ; Mato, Virginia ; Fonseca, Eduardo ; Kandouz, Mustapha ; Blanco, Alfonso ; Caeiro, José Ramón ; Mayán, María D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-355543aea57cbf083aa5a8fa166617f12178d752d8da50d0303e52cd1c25a92e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Antirheumatic Agents - isolation & purification</topic><topic>Antirheumatic Agents - pharmacology</topic><topic>Cartilage, Articular - drug effects</topic><topic>Cartilage, Articular - metabolism</topic><topic>Cartilage, Articular - pathology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line</topic><topic>Cellular Microenvironment</topic><topic>Cellular Senescence - drug effects</topic><topic>Chondrocytes - drug effects</topic><topic>Chondrocytes - metabolism</topic><topic>Chondrocytes - pathology</topic><topic>Chondrogenesis - drug effects</topic><topic>Collagen Type II - metabolism</topic><topic>Connexin 43 - genetics</topic><topic>Connexin 43 - metabolism</topic><topic>Female</topic><topic>Fruit</topic><topic>Humans</topic><topic>Iridoids - isolation & purification</topic><topic>Iridoids - pharmacology</topic><topic>Male</topic><topic>NF-kappa B - metabolism</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Olea - chemistry</topic><topic>Osteoarthritis - drug therapy</topic><topic>Osteoarthritis - genetics</topic><topic>Osteoarthritis - metabolism</topic><topic>Osteoarthritis - pathology</topic><topic>Osteogenesis - drug effects</topic><topic>Polyphenols - isolation & purification</topic><topic>Polyphenols - pharmacology</topic><topic>Priority Research Paper</topic><topic>Regeneration - drug effects</topic><topic>Signal Transduction</topic><topic>Twist-Related Protein 1 - genetics</topic><topic>Twist-Related Protein 1 - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Varela-Eirín, Marta</creatorcontrib><creatorcontrib>Carpintero-Fernández, Paula</creatorcontrib><creatorcontrib>Sánchez-Temprano, Agustín</creatorcontrib><creatorcontrib>Varela-Vázquez, Adrián</creatorcontrib><creatorcontrib>Paíno, Carlos Luis</creatorcontrib><creatorcontrib>Casado-Díaz, Antonio</creatorcontrib><creatorcontrib>Continente, Alfonso Calañas</creatorcontrib><creatorcontrib>Mato, Virginia</creatorcontrib><creatorcontrib>Fonseca, Eduardo</creatorcontrib><creatorcontrib>Kandouz, Mustapha</creatorcontrib><creatorcontrib>Blanco, Alfonso</creatorcontrib><creatorcontrib>Caeiro, José Ramón</creatorcontrib><creatorcontrib>Mayán, María D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging (Albany, NY.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Varela-Eirín, Marta</au><au>Carpintero-Fernández, Paula</au><au>Sánchez-Temprano, Agustín</au><au>Varela-Vázquez, Adrián</au><au>Paíno, Carlos Luis</au><au>Casado-Díaz, Antonio</au><au>Continente, Alfonso Calañas</au><au>Mato, Virginia</au><au>Fonseca, Eduardo</au><au>Kandouz, Mustapha</au><au>Blanco, Alfonso</au><au>Caeiro, José Ramón</au><au>Mayán, María D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis</atitle><jtitle>Aging (Albany, NY.)</jtitle><addtitle>Aging (Albany NY)</addtitle><date>2020-08-03</date><risdate>2020</risdate><volume>12</volume><issue>16</issue><spage>15882</spage><epage>15905</epage><pages>15882-15905</pages><issn>1945-4589</issn><eissn>1945-4589</eissn><abstract>Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our
results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>32745074</pmid><doi>10.18632/aging.103801</doi><tpages>24</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Antirheumatic Agents - isolation & purification Antirheumatic Agents - pharmacology Cartilage, Articular - drug effects Cartilage, Articular - metabolism Cartilage, Articular - pathology Cell Differentiation - drug effects Cell Line Cellular Microenvironment Cellular Senescence - drug effects Chondrocytes - drug effects Chondrocytes - metabolism Chondrocytes - pathology Chondrogenesis - drug effects Collagen Type II - metabolism Connexin 43 - genetics Connexin 43 - metabolism Female Fruit Humans Iridoids - isolation & purification Iridoids - pharmacology Male NF-kappa B - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism Olea - chemistry Osteoarthritis - drug therapy Osteoarthritis - genetics Osteoarthritis - metabolism Osteoarthritis - pathology Osteogenesis - drug effects Polyphenols - isolation & purification Polyphenols - pharmacology Priority Research Paper Regeneration - drug effects Signal Transduction Twist-Related Protein 1 - genetics Twist-Related Protein 1 - metabolism |
| title | Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
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