# Differential Roles of Collagen V in Establishing the Regional Properties in Mature and Aging Supraspinatus Tendons

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $225,256

## Abstract

Abstract from Parent Grant
Rotator cuff disorders of the shoulder are particularly devastating in the aging population with tears present in
50% of people over 60. Specific development and maturation processes, along with cues from the mechanical
loading environment, generate and remodel tendon structure and composition throughout life. These
processes are regionally-dependent, suggesting a complex spatially-dependent regulation of tissue
homeostasis. During aging, normal maturation processes and mechanical influences can result in
accumulation of sub-rupture damage and ultimately to tendon degeneration. The focus of this application is to
determine the mechanisms by which this might occur. The development of tendon structure is dependent upon
collagen I assembly into fibrils and higher order assemblies. This process is controlled by interactions involving
collagen V, a quantitatively minor yet critical regulatory component of tendon. Recent studies demonstrated
that altered fibril/fiber structure due to decreased collagen V content results in an inferior dynamic response to
load and inferior macroscale function. Furthermore, there was a differential regulation of structure by collagen
V at the insertion site and midsubstance of the supraspinatus tendon. The overall objective of this proposal is
to elucidate the differential regulatory role(s) of collagen V at the insertion site and midsubstance of the
supraspinatus tendon both at maturity and during the aging process. Our general hypothesis is that regulation
involving collagen V changes with aging. This results in site-specific regulatory roles due to altered content and
distinct interactions resulting from differences in matrix molecules present and assembled at the two sites. We
will test this hypothesis using targeted collagen V mouse models, which will define the role of an abnormal
matrix in aging, as well as with novel collagen V inducible models, which will delineate the role of altered
collagen V expression in the progression of tendon aging. The specific aims are to: Aim 1: Define the site-
specific alterations in structure, composition, dynamic processes and mechanical function during normal
supraspinatus tendon aging. Aim 2: Elucidate the site-specific differential roles of collagen V in determining
aging-associated declines in supraspinatus tendon properties. Aim 3: Delineate site-specific hierarchical
structure-function relationships as a function of collagen V content and aging utilizing sophisticated multiple
regression models. An innovative approach using targeted and inducible mouse models will define the
regulatory roles of collagen V during aging and in the establishment of regionally-dependent properties. This
approach will be coupled with sophisticated and innovative measures of mechanical (including fatigue) and
organizational properties, together with compositional profiles, to derive a mechanistic understanding of the
governing processes.

## Key facts

- **NIH application ID:** 10166009
- **Project number:** 3R01AR070750-04S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** LOUIS J SOSLOWSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $225,256
- **Award type:** 3
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166009

## Citation

> US National Institutes of Health, RePORTER application 10166009, Differential Roles of Collagen V in Establishing the Regional Properties in Mature and Aging Supraspinatus Tendons (3R01AR070750-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166009. Licensed CC0.

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