THE ROLE OF NON-MUSCLE MYOSIN IN TENDON AND ATTACHMENT UNIT FORMATION AND MATURATION
type: CreativeWork
description: Mechanical force via muscle contraction is critical for the development and maturation of tendons and their integration with the adjacent bone through a specialized tissue known as an attachment unit. The mechanisms by which applied loads regulate tendon and attachment unit biology are not well understood, contributing to poor clinical outcomes for tendon pathologies. Actomyosin contractility, powered by non-muscle myosin (NM-II), generates contractile forces and transduces signals from applied loads to the nucleus, supporting critical cellular functions such as division, migration, mechanosignaling, and cytoskeletal organization. Given the importance of loading on tendon biology and NM-II’s central role in regulating cytoskeletal tension, we hypothesized that NM-II-mediated actomyosin contractility is critical to the formation and maintenance of tendons and their attachments to bone. To test this hypothesis, we generated cell-lineage specific transgenic knockout mice to specifically delete NM-II in Prrx1 (limb mesenchyme) or Scx (tenogenic) lineage cells. In Chapter 2, we found that deletion of the predominant NM-II isoforms, NM-IIA (Myh9 gene) and NMII-B (Myh10 gene) affected both the formation and maturation of the attachment unit. In particular, the initial formation of the deltoid tuberosity (DT) attachment unit failed in limb mesenchyme lacking one copy of Myh9 and both copies of Myh10. Even in genotypes where the DT formed, there were notable alterations in both the size and shape of this tissue. We also identified a cell-lineage specific role for NM-II in regulating DT maturation, as deletion of both Myh9 and Myh10 in Scx-lineage cells (“Myosin dKO”) similarly affected DT morphology. In Chapter 3, we assessed the role of NM-II in the tendon midsubstance and found that NM-II-mediated contractility is critical for proper tendon growth and maintenance. In Myosin dKO tendons, lateral tendon growth was significantly reduced, corresponding with a decrease in colla…
abstract: Mechanical force via muscle contraction is critical for the development and maturation of tendons and their integration with the adjacent bone through a specialized tissue known as an attachment unit. The mechanisms by which applied loads regulate tendon and attachment unit biology are not well understood, contributing to poor clinical outcomes for tendon pathologies. Actomyosin contractility, powered by non-muscle myosin (NM-II), generates contractile forces and transduces signals from applied loads to the nucleus, supporting critical cellular functions such as division, migration, mechanosignaling, and cytoskeletal organization. Given the importance of loading on tendon biology and NM-II’s central role in regulating cytoskeletal tension, we hypothesized that NM-II-mediated actomyosin contractility is critical to the formation and maintenance of tendons and their attachments to bone. To test this hypothesis, we generated cell-lineage specific transgenic knockout mice to specifically delete NM-II in Prrx1 (limb mesenchyme) or Scx (tenogenic) lineage cells. In Chapter 2, we found that deletion of the predominant NM-II isoforms, NM-IIA (Myh9 gene) and NMII-B (Myh10 gene) affected both the formation and maturation of the attachment unit. In particular, the initial formation of the deltoid tuberosity (DT) attachment unit failed in limb mesenchyme lacking one copy of Myh9 and both copies of Myh10. Even in genotypes where the DT formed, there were notable alterations in both the size and shape of this tissue. We also identified a cell-lineage specific role for NM-II in regulating DT maturation, as deletion of both Myh9 and Myh10 in Scx-lineage cells (“Myosin dKO”) similarly affected DT morphology. In Chapter 3, we assessed the role of NM-II in the tendon midsubstance and found that NM-II-mediated contractility is critical for proper tendon growth and maintenance. In Myosin dKO tendons, lateral tendon growth was significantly reduced, corresponding with a decrease in colla…
author: Evans, Mary, Katharine
language: en
keywords: Engineering, Biology, Medicine and Health Sciences
date published: 2025
date modified: 2026-07-24T03:46:22Z
provider: University of Pennsylvania
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Pennsylvania