Universität zu Köln

Izu, Yayoi ORCID: 0000-0003-1813-6697, Adams, Sheila M., Connizzo, Brianne K., Beason, David P., Soslowsky, Louis J., Koch, Manuel ORCID: 0000-0002-2962-7814 and Birk, David E. (2021). Collagen XII mediated cellular and extracellular mechanisms regulate establishment of tendon structure and function. Matrix Biol., 95. S. 52 - 68. AMSTERDAM: ELSEVIER. ISSN 1569-1802

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Abstract

Tendons have a uniaxially aligned structure with a hierarchical organization of collagen fibrils crucial for tendon function. Collagen XII is expressed in tendons and has been implicated in the regulation of fibrillogenesis. It is a non-fibrillar collagen belonging to the Fibril-Associated Collagens with Interrupted Triple Helices (FACIT) family. Mutations in COL12A1 cause myopathic Ehlers Danlos Syndrome with a clinical phenotype involving both joints and tendons supporting critical role(s) for collagen XII in tendon development and function. Here we demonstrate the molecular function of collagen XII during tendon development using a Col12a1 null mouse model. Col12a1 deficiency altered tenocyte shape, formation of interacting cell processes, and organization resulting in impaired cell-cell communication and disruption of hierarchal structure as well as decreased tissue stiffness. Immuno-localization revealed that collagen XII accumulated on the tenocyte surface and connected adjacent tenocytes by building matrix bridges between the cells, suggesting that collagen XII regulates intercellular communication. In addition, there was a decrease in fibrillar collagen I in collagen XII deficient tenocyte cultures compared with controls suggesting collagen XII signaling specifically alters tenocyte biosynthesis. This suggests that collagen XII provides feedback to tenocytes regulating extracellular collagen I. Together, the data indicate dual roles for collagen XII in determination of tendon structure and function. Through association with fibrils it functions in fibril packing, fiber assembly and stability. In addition, collagen XII influences tenocyte organization required for assembly of higher order structure; intercellular communication necessary to coordinate long range order and feedback on tenocytes influencing collagen synthesis. Integration of both regulatory roles is required for the acquisition of hierarchal structure and mechanical properties. (C) 2020 The Authors. Published by Elsevier B.V.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Izu, Yayoi UNSPECIFIED orcid.org/0000-0003-1813-6697 UNSPECIFIED Adams, Sheila M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Connizzo, Brianne K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beason, David P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Soslowsky, Louis J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Birk, David E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-587759
DOI:	10.1016/j.matbio.2020.10.004
Journal or Publication Title:	Matrix Biol.
Volume:	95
Page Range:	S. 52 - 68
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1569-1802
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TISSUE-SPECIFIC EXPRESSION; DIFFERENTIAL EXPRESSION; SPLICE VARIANTS; MATRIX; FIBRIL; DECORIN; MORPHOGENESIS; FIBRILLOGENESIS; PROTEOGLYCANS; COMPARTMENTS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58775