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Spironolactone (SP) has been widely used as a diuretic in clinical practice. Recently, SP has shown anti\u2010inflammatory features in several diseases. Tendon\u2010derived stem cells (TDSCs), a subset cell type from tendon tissue possessing clonogenic capacity, play a vital role in the pathological process of tendinopathy. In the present study, the protective effect of SP on TDSCs was demonstrated under simulated tendinopathy conditions both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. SP contributed to the maintenance of TDSC\u2010specific genes or proteins, while suppressing the interleukin\u2010 (IL\u2010) 1<jats:italic>\u03b2<\/jats:italic>\u2010induced overexpression of inflammation\u2010mediated factors. Additionally, IL\u20101<jats:italic>\u03b2<\/jats:italic>\u2010induced cellular senescence in TDSCs was inhibited, while autophagy was enhanced, as determined via <jats:italic>\u03b2<\/jats:italic>\u2010galactosidase activity, western blot (WB), and quantitative real\u2010time polymerase chain reaction analysis. With the aid of several emerging bioinformatics tools, the mitogen\u2010activated protein kinase (MAPK) pathway likely participated in the effect of SP, which was further validated through WB analysis and the use of MAPK agonist. Immunofluorescence analysis and an NF\u2010<jats:italic>\u03ba<\/jats:italic>B agonist were used to confirm the inhibitory effect of SP on IL\u20101<jats:italic>\u03b2<\/jats:italic>\u2010induced activation of the NF\u2010<jats:italic>\u03ba<\/jats:italic>B pathway. X\u2010ray, immunofluorescence, immunohistochemistry, hematoxylin and eosin staining, histological grades, and Masson staining showed that SP ameliorated tendinopathy in an Achilles tenotomy (AT) rat model <jats:italic>in vivo<\/jats:italic>. This work elucidates the protective role of SP on the pathological process of tendinopathy both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, indicating a potential therapeutic strategy for tendinopathy treatment.<\/jats:p>","DOI":"10.1155\/2021\/5519587","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T03:05:07Z","timestamp":1625108707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Spironolactone Ameliorates Senescence and Calcification by Modulating Autophagy in Rat Tendon\u2010Derived Stem Cells via the NF\u2010<i>\u03ba<\/i>B\/MAPK Pathway"],"prefix":"10.1155","volume":"2021","author":[{"given":"Kai","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-922X","authenticated-orcid":false,"given":"Changjian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-5347","authenticated-orcid":false,"given":"Diana","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0250-4774","authenticated-orcid":false,"given":"Mengyao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2108-0380","authenticated-orcid":false,"given":"Xing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4291-5674","authenticated-orcid":false,"given":"Yuzhe","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-560X","authenticated-orcid":false,"given":"Safwat Adel Abdo","family":"Moqbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1605-8093","authenticated-orcid":false,"given":"Chiyuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2561-6069","authenticated-orcid":false,"given":"Lidong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"e_1_2_10_1_2","article-title":"Tendinopathy","volume":"7","author":"Millar N. 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