Regulatory Roles of Type III Collagen in Tendon Development and Healing Margaret Kathryn Tamburro

Format:

Book

Thesis/Dissertation

Author/Creator:

Tamburro, Margaret Kathryn, author.

Contributor:

University of Pennsylvania, degree granting institution.

University of Pennsylvania. Bioengineering., degree granting institution.

Language:

English

Subjects (All):

Bioengineering.

Cellular biology.

Molecular biology.

0202.

0379.

0307.

Local Subjects:

Bioengineering.

Cellular biology.

Molecular biology.

0202.

0379.

0307.

Genre:

Academic theses

Physical Description:

1 electronic resource (146 pages)

Contained In:

Dissertations Abstracts International 87-03B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2025

Language Note:

English

Summary:

Tendons transmit forces generated by muscles into skeletal movement. The specialized tendon extracellular matrix, comprised of highly-aligned type I collagen (COL1), imparts resistance to tensile strain to enable this important function. However, after tendon injury, inadequate physiologic healing creates a type III collagen (COL3)-rich fibrovascular scar that fails to recapitulate native tendon structure causing substantial functional deficits. Despite the sizeable clinical burden of poor tendon healing, contributing mechanisms are unelucidated and therapeutic strategies are lacking. Defining regulatory processes involved in tendon matrix formation is a foundational step for guiding treatment approaches that seek to recapitulate healthy tendon after injury.COL3, encoded by the Col3a1 gene, is a compelling candidate for regulation of tendon matrix formation. Both developing and healing tendons are COL3-rich, and COL3 regulates matrix and cell behavior in other COL1- and fibroblast-rich tissues. Therefore, the objective of this dissertation was to define and juxtapose the regulatory roles of COL3 in formation of tendon matrix in three high COL3 contexts: young adult tendon injury (Aim 1, Chapter 2), neonatal tendon development (Aim 2, Chapter 2), and neonatal tendon healing (Aim 3, Chapter 4). Each aim capitalized on transgenic mouse models to reduce Col3a1 expression and investigated consequential matrix, cell, and mechanical impacts of COL3 loss. In Aim 1, reduction of Col3a1 expression at the time of mature, young adult patellar tendon injury had negligible influences on healing outcomes, challenging the classical association of COL3 and poor tendon healing. In Aim 2, constitutive, tendon-targeted reduction of Col3a1 expression during neonatal tendon development caused impaired matrix and mechanical development, revealing a role for COL3 in regulating patellar tendon development, particularly in the distal tendon insertion. Finally, in Aim 3, constitutive, tendon-targeted reduction of Col3a1 during neonatal tendon healing impaired matrix formation and mechanical recovery in early healing but did not influence late healing outcomes. Collectively, this work informs strategies that seek to mimic tendon matrix formation and challenges existing paradigms to make way for advanced investigations of mechanisms of tendon healing

Notes:

Source: Dissertations Abstracts International, Volume: 87-03, Section: B.

Advisors: Soslowsky, Louis J. Committee members: Volk, Susan W.; Dyment, Nathaniel A.; Rodeo, Scott A.; Brass, Lawrence F.

Ph.D. University of Pennsylvania 2025

Local Notes:

School code: 0175

ISBN:

9798291598382

Access Restriction:

Restricted for use by site license