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However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G\u2010) actin\u2010binding transcription factor, myocardin\u2010related transcription factor\u2010a (MRTF). We determined that decreasing the proportion of G\u2010actin in tenocytes by treatment with TGF\u03b21 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G\u2010actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis\u2010like phenotype. To parse out the effects of F\u2010actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Exposure of cells to cytochalasin D increases the proportion of G\u2010actin in tenocytes. However, as compared to latrunculin A, cytochalasin D has a differential effect on MRTF localization by increasing nuclear MRTF. This led to an opposing effect on the regulation of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and \u03b1\u2010smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.<\/jats:p>","DOI":"10.1002\/cm.21962","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T07:30:32Z","timestamp":1732692632000},"page":"539-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin\u2010Related Transcription Factor\u2010A"],"prefix":"10.1002","volume":"82","author":[{"given":"Valerie C.","family":"West","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Delaware  Newark Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaelyn E.","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Delaware  Newark Delaware 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