# Collagen III differential roles in temporal regulation of tendon healing across ages

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $337,434

## Abstract

Tendons can withstand large forces due to a highly aligned, dense collagen matrix. However, their low
cellularity and relative inability to recruit reparative cells post-injury, as well as susceptibility to excessive
scarring results in loss of tendon structure and mechanical function. Type I collagen (Col1) is the primary
collagen of healthy tendon and type III collagen (Col3) is a minor constituent that increases in response to
injury. In other Col1-rich tissues such as skin and bone, Col3 directs reparative cell activities by regulating
early cellular infiltration to promote healing, as well as collagen deposition, architecture and crosslink
formation, supporting an early critical role of Col3 in wound healing, which has not been studied in tendon.
Adding to the importance of understanding a role for Col3 in tendon, Col3 levels in aging tissues are reduced
and in aged tendon, we have shown inferior healing which raises the possibility that age-induced Col3 loss
increases susceptibility to poor tendon healing in aging populations. While Col3 may orchestrate cellular
activities and fate that are critical for an optimal reparative response post-injury at early stages in tendon, its
persistent expression in the remodeling phase may compromise the desired healing response. Therefore, our
overall objective is to delineate mechanisms by which the temporal expression of Col3 modulates the injury
response throughout tendon healing, as well as its differential effect throughout aging. Specifically, we will test
the hypothesis that Col3 is crucial for early tendon healing, but that its continued expression during remodeling
is detrimental. To test this, we generated a novel inducible Col3 deficient (i.e., Col3a1F/+, Col3a1F/F) mouse
model to determine the dose-dependent effects of Col3 by temporal targeting of Col3. Using this approach, we
will define the regulatory roles of Col3 throughout tendon healing at the time of injury, during the early
proliferative phase, and during remodeling. In addition, by knockdown of Col3 in young, middle-aged, and old
animals, we will evaluate the effects of aging on tendon healing with altered Col3. Understanding the role of
Col3 throughout healing will lead to clinically relevant insights to improve outcomes following tendon injury in
patients of varying ages. The study aims are: Aim 1: To define the age-sensitive mechanistic role(s) of Col3
throughout tendon healing by knocking down Col3 at the time of tendon injury. Aim 2: To elucidate the age-
sensitive mechanistic role(s) of Col3 in directing reparative cell activities and prolonged effects of knocking
down Col3 during the proliferative phase of tendon healing. Aim 3: To define the age-sensitive mechanistic
role(s) of Col3 in tendon repair by knocking down Col3 during the remodeling phase of tendon healing. This
study will define the critical temporal roles of Col3 in response to tendon injury throughout aging. We will utilize
a novel mouse model coupled with rigor...

## Key facts

- **NIH application ID:** 10828865
- **Project number:** 5R01AR080029-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** LOUIS J SOSLOWSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $337,434
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828865

## Citation

> US National Institutes of Health, RePORTER application 10828865, Collagen III differential roles in temporal regulation of tendon healing across ages (5R01AR080029-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10828865. Licensed CC0.

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