Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A
| Author(s) | West, Valerie C. | |
| Author(s) | Owen, Kaelyn E. | |
| Author(s) | Inguito, Kameron L. | |
| Author(s) | Ebron, Karl Matthew M. | |
| Author(s) | Reiner, Tori N. | |
| Author(s) | Mirack, Chloe E. | |
| Author(s) | Le, Christian H. | |
| Author(s) | Marqueti, Rita de Cassia | |
| Author(s) | Snipes, Steven | |
| Author(s) | Mousavizadeh, Rouhollah | |
| Author(s) | King, Rylee E. | |
| Author(s) | Elliott, Dawn M. | |
| Author(s) | Parreno, Justin | |
| Date Accessioned | 2025-02-14T14:26:53Z | |
| Date Available | 2025-02-14T14:26:53Z | |
| Publication Date | 2024-11-27 | |
| Description | This is the peer reviewed version of the following article: West, V.C., Owen, K.E., Inguito, K.L., Ebron, K.M.M., Reiner, T.N., Mirack, C.E., Le, C.H., de Cassia Marqueti, R., Snipes, S., Mousavizadeh, R., King, R.E., Elliott, D.M. and Parreno, J. (2025), Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A. Cytoskeleton. https://doi.org/10.1002/cm.21962, which has been published in final form at https://doi.org/10.1002/cm.21962. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. © 2024 Wiley Periodicals LLC. This article will be embargoed until 11/27/2025. | |
| Abstract | The actin cytoskeleton is a potent regulator of tenocyte homeostasis. 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-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFβ1 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-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Exposure of cells to cytochalasin D increases the proportion of G-actin 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 α-smooth 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. | |
| Sponsor | This research was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant R01AR080059 as well as from the Delaware Center for Musculoskeletal Research from the National Institutes of Health's National Institute of General Medical Sciences under grant number P20GM139760. This publication was made possible by the Delaware INBRE program, supported by a grant from the National Institute of General Medical Sciences—NIGMS (P20GM103446) from the National Institutes of Health and the State of Delaware. K.L.I. and K.M.M.E. was supported by the University of Delaware Summer Scholars Program. R.M. was supported by an Orthopaedic Research Society Collaborative Exchange Grant. | |
| Citation | West, V.C., Owen, K.E., Inguito, K.L., Ebron, K.M.M., Reiner, T.N., Mirack, C.E., Le, C.H., de Cassia Marqueti, R., Snipes, S., Mousavizadeh, R., King, R.E., Elliott, D.M. and Parreno, J. (2025), Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A. Cytoskeleton. https://doi.org/10.1002/cm.21962 | |
| ISSN | 1949-3592 | |
| URL | https://udspace.udel.edu/handle/19716/35808 | |
| Language | en_US | |
| Publisher | Cytoskeleton | |
| Title | Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A | |
| Type | Article |
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