Universität zu Köln

Kronenberg, Daniel ORCID: 0000-0001-6807-7328, Michel, Philipp A., Hochstrat, Eva, Wei, Ma, Brinckmann, Juergen, Mueller, Marcus, Frank, Andre ORCID: 0000-0001-7099-9719, Hansen, Uwe, Eckes, Beate and Stange, Richard ORCID: 0000-0003-0807-3151 (2020). Increased Collagen Turnover Impairs Tendon Microstructure and Stability in Integrin alpha 2 beta 1-Deficient Mice. Int. J. Mol. Sci., 21 (8). BASEL: MDPI. ISSN 1422-0067

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Abstract

Integrins are a family of transmembrane proteins, involved in substrate recognition and cell adhesion in cross-talk with the extra cellular matrix. In this study, we investigated the influence of integrin alpha 2 beta 1 on tendons, another collagen type I-rich tissue of the musculoskeletal system. Morphological, as well as functional, parameters were analyzed in vivo and in vitro, comparing wild-type against integrin alpha 2 beta 1 deficiency. Tenocytes lacking integrin alpha 2 beta 1 produced more collagen in vitro, which is similar to the situation in osseous tissue. Fibril morphology and biomechanical strength proved to be altered, as integrin alpha 2 beta 1 deficiency led to significantly smaller fibrils as well as changes in dynamic E-modulus in vivo. This discrepancy can be explained by a higher collagen turnover: integrin alpha 2 beta 1-deficient cells produced more matrix, and tendons contained more residual C-terminal fragments of type I collagen, as well as an increased matrix metalloproteinase-2 activity. A greatly decreased percentage of non-collagenous proteins may be the cause of changes in fibril diameter regulation and increased the proteolytic degradation of collagen in the integrin-deficient tendons. The results reveal a significant impact of integrin alpha 2 beta 1 on collagen modifications in tendons. Its role in tendon pathologies, like chronic degradation, will be the subject of future investigations.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kronenberg, Daniel UNSPECIFIED orcid.org/0000-0001-6807-7328 UNSPECIFIED Michel, Philipp A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hochstrat, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Wei, Ma UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinckmann, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Andre UNSPECIFIED orcid.org/0000-0001-7099-9719 UNSPECIFIED Hansen, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Stange, Richard UNSPECIFIED orcid.org/0000-0003-0807-3151 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-338183
DOI:	10.3390/ijms21082835
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	8
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-ADHESION; ANGIOGENESIS; FIBROBLASTS; EXPRESSION Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33818