Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway
Tendinopathy is a common musculoskeletal system disorder in sports medicine, but regeneration ability of injury tendon is limited. Tendon stem cells (TSCs) have shown the definitive treatment evidence for tendinopathy and tendon injuries due to their tenogenesis capacity. Aspirin, as the representat...
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| Veröffentlicht in: | Journal of cellular physiology 2020-05, Vol.235 (5), p.4778-4789 |
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| creator | Wang, Yunjiao He, Gang Tang, Hong Shi, Youxing Zhu, Min Kang, Xia Bian, Xuting Lyu, Jingtong Zhou, Mei Yang, Mingyu Mu, Miduo Chen, Wan Zhou, Binghua Yuan, Chengsong Zhang, Jiqiang Tang, Kanglai |
| description | Tendinopathy is a common musculoskeletal system disorder in sports medicine, but regeneration ability of injury tendon is limited. Tendon stem cells (TSCs) have shown the definitive treatment evidence for tendinopathy and tendon injuries due to their tenogenesis capacity. Aspirin, as the representative of nonsteroidal anti‐inflammatory drugs for its anti‐inflammatory and analgestic actions, has been commonly used in treating tendinopathy in clinical, but the effect of aspirin on tenogenesis of TSCs is unclear. We hypothesized that aspirin could promote injury tendon healing through inducing TSCs tenogenesis. The aim of the present study is to make clear the effect of aspirin on TSC tenogenesis and tendon healing in tendinopathy, and thus provide new treatment evidence and strategy of aspirin for clinical practice. First, TSCs were treated with aspirin under tenogenic medium for 3, 7, and 14 days. Sirius Red staining was performed to observe the TSC differentiation. Furthermore, RNA sequencing was utilized to screen out different genes between the induction group and aspirin treatment group. Then, we identified the filtrated molecules and compared their effect on tenogenesis and related signaling pathway. At last, we constructed the tendinopathy model and compared biomechanical changes after aspirin intake. From the results, we found that aspirin promoted tenogenesis of TSCs. RNA sequencing showed that growth differentiation factor 6 (GDF6), GDF7, and GDF11 were upregulated in induction medium with the aspirin group compared with the induction medium group. GDF7 increased tenogenesis and activated Smad1/5 signaling. In addition, aspirin increased the expression of TNC, TNMD, and Scx and biomechanical properties of the injured tendon. In conclusion, aspirin promoted TSC tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.
Aspirin promoted tendon stem cells tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries. |
| doi_str_mv | 10.1002/jcp.29355 |
| format | Article |
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Aspirin promoted tendon stem cells tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.29355</identifier><identifier>PMID: 31637734</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Achilles Tendon - drug effects ; Achilles Tendon - metabolism ; Achilles Tendon - pathology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Aspirin ; Aspirin - pharmacology ; Biomechanics ; Bone Morphogenetic Proteins - genetics ; Bone Morphogenetic Proteins - metabolism ; Cell differentiation ; Cell Differentiation - drug effects ; Cells, Cultured ; Differentiation ; Disease Models, Animal ; Gene sequencing ; Growth Differentiation Factors - genetics ; Growth Differentiation Factors - metabolism ; Healing ; Inflammation ; Injuries ; Injury prevention ; Male ; Mechanical properties ; Musculoskeletal system ; NSAIDs ; Rats, Sprague-Dawley ; Regeneration ; Ribonucleic acid ; RNA ; Signal Transduction ; Signaling ; Smad1 Protein - genetics ; Smad1 Protein - metabolism ; Smad5 Protein - genetics ; Smad5 Protein - metabolism ; Sports medicine ; stem cell differentiation ; Stem cells ; Stem Cells - drug effects ; Stem Cells - metabolism ; Stem Cells - pathology ; Tendinopathy - drug therapy ; Tendinopathy - genetics ; Tendinopathy - metabolism ; Tendinopathy - pathology ; tendon injury healing ; Wound Healing - drug effects</subject><ispartof>Journal of cellular physiology, 2020-05, Vol.235 (5), p.4778-4789</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><rights>2020 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-18d872a555640722c49a602f0f489987b56ca7af8e65b97ea672e8e8900dc3253</citedby><cites>FETCH-LOGICAL-c3535-18d872a555640722c49a602f0f489987b56ca7af8e65b97ea672e8e8900dc3253</cites><orcidid>0000-0003-1108-7079</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.29355$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.29355$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31637734$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yunjiao</creatorcontrib><creatorcontrib>He, Gang</creatorcontrib><creatorcontrib>Tang, Hong</creatorcontrib><creatorcontrib>Shi, Youxing</creatorcontrib><creatorcontrib>Zhu, Min</creatorcontrib><creatorcontrib>Kang, Xia</creatorcontrib><creatorcontrib>Bian, Xuting</creatorcontrib><creatorcontrib>Lyu, Jingtong</creatorcontrib><creatorcontrib>Zhou, Mei</creatorcontrib><creatorcontrib>Yang, Mingyu</creatorcontrib><creatorcontrib>Mu, Miduo</creatorcontrib><creatorcontrib>Chen, Wan</creatorcontrib><creatorcontrib>Zhou, Binghua</creatorcontrib><creatorcontrib>Yuan, Chengsong</creatorcontrib><creatorcontrib>Zhang, Jiqiang</creatorcontrib><creatorcontrib>Tang, Kanglai</creatorcontrib><title>Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Tendinopathy is a common musculoskeletal system disorder in sports medicine, but regeneration ability of injury tendon is limited. Tendon stem cells (TSCs) have shown the definitive treatment evidence for tendinopathy and tendon injuries due to their tenogenesis capacity. Aspirin, as the representative of nonsteroidal anti‐inflammatory drugs for its anti‐inflammatory and analgestic actions, has been commonly used in treating tendinopathy in clinical, but the effect of aspirin on tenogenesis of TSCs is unclear. We hypothesized that aspirin could promote injury tendon healing through inducing TSCs tenogenesis. The aim of the present study is to make clear the effect of aspirin on TSC tenogenesis and tendon healing in tendinopathy, and thus provide new treatment evidence and strategy of aspirin for clinical practice. First, TSCs were treated with aspirin under tenogenic medium for 3, 7, and 14 days. Sirius Red staining was performed to observe the TSC differentiation. Furthermore, RNA sequencing was utilized to screen out different genes between the induction group and aspirin treatment group. Then, we identified the filtrated molecules and compared their effect on tenogenesis and related signaling pathway. At last, we constructed the tendinopathy model and compared biomechanical changes after aspirin intake. From the results, we found that aspirin promoted tenogenesis of TSCs. RNA sequencing showed that growth differentiation factor 6 (GDF6), GDF7, and GDF11 were upregulated in induction medium with the aspirin group compared with the induction medium group. GDF7 increased tenogenesis and activated Smad1/5 signaling. In addition, aspirin increased the expression of TNC, TNMD, and Scx and biomechanical properties of the injured tendon. In conclusion, aspirin promoted TSC tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.
Aspirin promoted tendon stem cells tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.</description><subject>Achilles Tendon - drug effects</subject><subject>Achilles Tendon - metabolism</subject><subject>Achilles Tendon - pathology</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Aspirin</subject><subject>Aspirin - pharmacology</subject><subject>Biomechanics</subject><subject>Bone Morphogenetic Proteins - genetics</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Differentiation</subject><subject>Disease Models, Animal</subject><subject>Gene sequencing</subject><subject>Growth Differentiation Factors - genetics</subject><subject>Growth Differentiation Factors - metabolism</subject><subject>Healing</subject><subject>Inflammation</subject><subject>Injuries</subject><subject>Injury prevention</subject><subject>Male</subject><subject>Mechanical properties</subject><subject>Musculoskeletal system</subject><subject>NSAIDs</subject><subject>Rats, Sprague-Dawley</subject><subject>Regeneration</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Smad1 Protein - genetics</subject><subject>Smad1 Protein - metabolism</subject><subject>Smad5 Protein - genetics</subject><subject>Smad5 Protein - metabolism</subject><subject>Sports medicine</subject><subject>stem cell differentiation</subject><subject>Stem cells</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - metabolism</subject><subject>Stem Cells - pathology</subject><subject>Tendinopathy - drug therapy</subject><subject>Tendinopathy - genetics</subject><subject>Tendinopathy - metabolism</subject><subject>Tendinopathy - pathology</subject><subject>tendon injury healing</subject><subject>Wound Healing - drug effects</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQhy0EokvhwAsgS1zgkK7_xHF8rLa0gCqBBJwjrzPOepXYwU5U7avwtDjNwgGJky3PN5_G80PoNSVXlBC2PZrxiikuxBO0oUTJoqwEe4o2uUYLJUp6gV6kdCSEKMX5c3TBacWl5OUG_bpOo4vO4zGGIUyQ8AQ-dOCdwa2zFiL4yenJBY-DXYptvqUJBmyg7xPWvsVWG9e7SZ_bW-fDqKfDCR9A9853eDrEMHcHHKGb-yx7fAJ8d3Mrt98G3dKtwMl1fqWX3gd9eomeWd0neHU-L9GP2w_fdx-L-y93n3bX94XhgouC1m0tmRZCVCWRjJlS6YowS2xZK1XLvaiMltrWUIm9kqAryaCGWhHSGs4Ev0TvVm9ewc8Z0tQMLi2f0x7CnBrGSd6VqjjL6Nt_0GOYYx57oQQvM0RUpt6vlIkhpQi2GaMbdDw1lDRLYE0OrHkMLLNvzsZ5P0D7l_yTUAa2K_Dgejj939R83n1dlb8BrtGg0w</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Wang, Yunjiao</creator><creator>He, Gang</creator><creator>Tang, Hong</creator><creator>Shi, Youxing</creator><creator>Zhu, Min</creator><creator>Kang, Xia</creator><creator>Bian, Xuting</creator><creator>Lyu, Jingtong</creator><creator>Zhou, Mei</creator><creator>Yang, Mingyu</creator><creator>Mu, Miduo</creator><creator>Chen, Wan</creator><creator>Zhou, Binghua</creator><creator>Yuan, Chengsong</creator><creator>Zhang, Jiqiang</creator><creator>Tang, Kanglai</creator><general>Wiley Subscription Services, Inc</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>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1108-7079</orcidid></search><sort><creationdate>202005</creationdate><title>Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway</title><author>Wang, Yunjiao ; He, Gang ; Tang, Hong ; Shi, Youxing ; Zhu, Min ; Kang, Xia ; Bian, Xuting ; Lyu, Jingtong ; Zhou, Mei ; Yang, Mingyu ; Mu, Miduo ; Chen, Wan ; Zhou, Binghua ; Yuan, Chengsong ; Zhang, Jiqiang ; Tang, Kanglai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3535-18d872a555640722c49a602f0f489987b56ca7af8e65b97ea672e8e8900dc3253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Achilles Tendon - drug effects</topic><topic>Achilles Tendon - metabolism</topic><topic>Achilles Tendon - pathology</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Aspirin</topic><topic>Aspirin - pharmacology</topic><topic>Biomechanics</topic><topic>Bone Morphogenetic Proteins - genetics</topic><topic>Bone Morphogenetic Proteins - metabolism</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cells, Cultured</topic><topic>Differentiation</topic><topic>Disease Models, Animal</topic><topic>Gene sequencing</topic><topic>Growth Differentiation Factors - genetics</topic><topic>Growth Differentiation Factors - metabolism</topic><topic>Healing</topic><topic>Inflammation</topic><topic>Injuries</topic><topic>Injury prevention</topic><topic>Male</topic><topic>Mechanical properties</topic><topic>Musculoskeletal system</topic><topic>NSAIDs</topic><topic>Rats, Sprague-Dawley</topic><topic>Regeneration</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Smad1 Protein - genetics</topic><topic>Smad1 Protein - metabolism</topic><topic>Smad5 Protein - genetics</topic><topic>Smad5 Protein - metabolism</topic><topic>Sports medicine</topic><topic>stem cell differentiation</topic><topic>Stem cells</topic><topic>Stem Cells - drug effects</topic><topic>Stem Cells - metabolism</topic><topic>Stem Cells - pathology</topic><topic>Tendinopathy - drug therapy</topic><topic>Tendinopathy - genetics</topic><topic>Tendinopathy - metabolism</topic><topic>Tendinopathy - pathology</topic><topic>tendon injury healing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yunjiao</creatorcontrib><creatorcontrib>He, Gang</creatorcontrib><creatorcontrib>Tang, Hong</creatorcontrib><creatorcontrib>Shi, Youxing</creatorcontrib><creatorcontrib>Zhu, Min</creatorcontrib><creatorcontrib>Kang, Xia</creatorcontrib><creatorcontrib>Bian, Xuting</creatorcontrib><creatorcontrib>Lyu, Jingtong</creatorcontrib><creatorcontrib>Zhou, Mei</creatorcontrib><creatorcontrib>Yang, Mingyu</creatorcontrib><creatorcontrib>Mu, Miduo</creatorcontrib><creatorcontrib>Chen, Wan</creatorcontrib><creatorcontrib>Zhou, Binghua</creatorcontrib><creatorcontrib>Yuan, Chengsong</creatorcontrib><creatorcontrib>Zhang, Jiqiang</creatorcontrib><creatorcontrib>Tang, Kanglai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yunjiao</au><au>He, Gang</au><au>Tang, Hong</au><au>Shi, Youxing</au><au>Zhu, Min</au><au>Kang, Xia</au><au>Bian, Xuting</au><au>Lyu, Jingtong</au><au>Zhou, Mei</au><au>Yang, Mingyu</au><au>Mu, Miduo</au><au>Chen, Wan</au><au>Zhou, Binghua</au><au>Yuan, Chengsong</au><au>Zhang, Jiqiang</au><au>Tang, Kanglai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2020-05</date><risdate>2020</risdate><volume>235</volume><issue>5</issue><spage>4778</spage><epage>4789</epage><pages>4778-4789</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Tendinopathy is a common musculoskeletal system disorder in sports medicine, but regeneration ability of injury tendon is limited. Tendon stem cells (TSCs) have shown the definitive treatment evidence for tendinopathy and tendon injuries due to their tenogenesis capacity. Aspirin, as the representative of nonsteroidal anti‐inflammatory drugs for its anti‐inflammatory and analgestic actions, has been commonly used in treating tendinopathy in clinical, but the effect of aspirin on tenogenesis of TSCs is unclear. We hypothesized that aspirin could promote injury tendon healing through inducing TSCs tenogenesis. The aim of the present study is to make clear the effect of aspirin on TSC tenogenesis and tendon healing in tendinopathy, and thus provide new treatment evidence and strategy of aspirin for clinical practice. First, TSCs were treated with aspirin under tenogenic medium for 3, 7, and 14 days. Sirius Red staining was performed to observe the TSC differentiation. Furthermore, RNA sequencing was utilized to screen out different genes between the induction group and aspirin treatment group. Then, we identified the filtrated molecules and compared their effect on tenogenesis and related signaling pathway. At last, we constructed the tendinopathy model and compared biomechanical changes after aspirin intake. From the results, we found that aspirin promoted tenogenesis of TSCs. RNA sequencing showed that growth differentiation factor 6 (GDF6), GDF7, and GDF11 were upregulated in induction medium with the aspirin group compared with the induction medium group. GDF7 increased tenogenesis and activated Smad1/5 signaling. In addition, aspirin increased the expression of TNC, TNMD, and Scx and biomechanical properties of the injured tendon. In conclusion, aspirin promoted TSC tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.
Aspirin promoted tendon stem cells tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31637734</pmid><doi>10.1002/jcp.29355</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-1108-7079</orcidid></addata></record> |
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| subjects | Achilles Tendon - drug effects Achilles Tendon - metabolism Achilles Tendon - pathology Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Aspirin Aspirin - pharmacology Biomechanics Bone Morphogenetic Proteins - genetics Bone Morphogenetic Proteins - metabolism Cell differentiation Cell Differentiation - drug effects Cells, Cultured Differentiation Disease Models, Animal Gene sequencing Growth Differentiation Factors - genetics Growth Differentiation Factors - metabolism Healing Inflammation Injuries Injury prevention Male Mechanical properties Musculoskeletal system NSAIDs Rats, Sprague-Dawley Regeneration Ribonucleic acid RNA Signal Transduction Signaling Smad1 Protein - genetics Smad1 Protein - metabolism Smad5 Protein - genetics Smad5 Protein - metabolism Sports medicine stem cell differentiation Stem cells Stem Cells - drug effects Stem Cells - metabolism Stem Cells - pathology Tendinopathy - drug therapy Tendinopathy - genetics Tendinopathy - metabolism Tendinopathy - pathology tendon injury healing Wound Healing - drug effects |
| title | Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway |
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