# Collagen XI and XI/V regulatory mechanisms in assembly of tendon hierarchical structure and acquisition of mechanical properties in development and injury response

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $322,453

## Abstract

The hierarchical establishment of tendon structure and function during development, maturation and healing is
dependent upon collagen I assembly into fibrils and higher order structures. The regulatory fibril-forming
collagens XI and V are essential in the regulation of fibril assembly and fiber organization, despite being
quantitatively minor components. Collagen XI is expressed during development, but is virtually absent in
mature tendons, while collagen V is expressed throughout development, maturation, and in mature tendon.
During the injury response there is a transient increase in collagen XI and sustained increase in collagen V
expression. Importantly, the clinical phenotype in patients with mutations in COL11A1 with Stickler's Syndrome
and COL5A1 with classic Ehlers Danlos Syndrome includes joint laxity involving tendons and ligaments. Also,
collagen XI and V genes are linked to tendinopathy while collagen V genes are linked to ACL rupture in
women. These findings support critical regulatory mechanisms for these collagens in the establishment of
tendon structure and function, re-establishment after injury, as well as alterations associated with pathologies
supporting our general hypothesis that collagen XI- and synergistic collagen XI/V-mediated mechanisms are
necessary for establishing tendon structure/function and that these mechanisms are recapitulated after injury.
Our specific aims are to: (Aim 1) Define the mechanism(s) involving collagen XI interactions and synergistic
collagen XI/V interactions regulating the hierarchical assembly of the tendon required for function. The
hypotheses are that establishment of initial tendon structure and function requires interactions involving
collagen XI while continued development and maturation require coordinate collagen XI and V interactions;
(Aim 2) Elucidate the regulatory mechanism(s) involving collagen XI and/or synergistic roles of collagens XI/V
in the tendon response to injury. The hypothesis is that regulatory mechanisms involved in the reacquisition of
tendon structure and function require coordinate collagen XI and XI/V expression. Specifically, altering
collagen XI or XI/V expression will cause an impairment of repair including fibril assembly, wound matrix
organization, and integration of new matrix into the surrounding unwounded matrix influencing structural
organization of the tendon and its mechanical properties. Collagen XI will influence the early stages of injury
response while synergistic collagen XI/V interactions will have a broad impact in all stages. Our
multidisciplinary approach will utilize novel mouse models to modulate collagen XI and XI/V expression
followed by a definition of the effects on the structural, macro-scale mechanical, fibril mechanical, and
compositional properties. These studies will define tendon-specific regulatory mechanisms involving collagens
XI and XI/V, providing a mechanistic understanding of the acquisition of tendon structure and function in...

## Key facts

- **NIH application ID:** 10172850
- **Project number:** 5R01AR073231-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** LOUIS J SOSLOWSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $322,453
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172850

## Citation

> US National Institutes of Health, RePORTER application 10172850, Collagen XI and XI/V regulatory mechanisms in assembly of tendon hierarchical structure and acquisition of mechanical properties in development and injury response (5R01AR073231-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10172850. Licensed CC0.

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