# The role of myosin II in tendon repair under glucose control

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $201,216

## Abstract

Tendon injury and disorders provide a severe negative impact on the economic cost and the ability to meet the
patients' occupational, recreational, and health activities. Despite continuous efforts to improve the therapeutic
modalities for tendon repair, truly effective and efficient therapies have not been established yet. Our long-term
goal is to understand the mechanisms underlying the limited regenerative potential of tendons and develop new
methods for stimulating tendon repair. Unlike embryonic and neonatal tendons, neo-formed tendons after injury
do not possess native tendon structure and mechanical properties. Healing tendons from scar with abnormal
mechanical properties. One of the key challenges for recovery of structure and function of injured tendons is how
to potentiate the reparative capacity of the tendon progenitor cells involved in tendon healing, including how to
stimulate their tenogenic differentiation and how to make them rebuild tendon matrix structure. The results from
clinical and translational studies indicate a close link between glucose metabolism and tendon healing capacity.
We have found that 2-deoxy glucose (2DG), an inhibitor of glucose, stimulated recovery of collagen fiber
alignment in injured tendons. Proteomics studies on the actions of 2DG on tendon healing demonstrated that
2DG stimulated the actin cytoskeletal signaling in injured tendons. Unexpectedly, we found that the mid-
substance of tendons expressed muscle type myosin II components but a strongly down-regulated expression
of these molecules when injured, whereas 2DG restored these changes.
Furthermore, injured tendon-derived progenitor cells responded to 2DG, up-regulated expression of muscle type
myosin light chains, and rearranged actin cytoskeletons. Previous studies have demonstrated that actin
cytoskeletal organization and myosin II activity are required for collagen fiber alignment. Taken together, we
hypothesize that upregulation of muscle type myosin II molecules in injured tendons may stimulate collagen fiber
alignment. Furthermore, that glucose controls the expression of muscle type myosin II molecules and the actin
cytoskeletal organization. To test these hypotheses, we propose two aims. In Aim 1, we will determine alterations
of myosin II molecules in tendons during injury, healing, and regeneration. Spatiotemporal changes in the myosin
II components (myosin heavy and light chains) will be defined in injured tendons using four mouse Achilles
tendon injury models. In Aim 2, we will determine the roles of muscle type of myosin II in injured tendon-derived
cells (inTPCs). InTPCs will be treated with 2DG in mono- or 3D-culture, and changes in the expression of myosin
II molecules, RhoA/Rac activity, collagen fiber alignment, and mechanical properties will be examined. In addition,
in the same model, the effects of gain- and loss-of-function of muscle myosin II molecules will be determined.
Best of our knowledge, it has not been known whether mu...

## Key facts

- **NIH application ID:** 10440751
- **Project number:** 1R21AR080996-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** MOTOMI ENOMOTO-IWAMOTO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,216
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440751

## Citation

> US National Institutes of Health, RePORTER application 10440751, The role of myosin II in tendon repair under glucose control (1R21AR080996-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10440751. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*