TY - JOUR
T1 - Increased collagen turnover impairs tendon microstructure and stability in integrin α2β1-deficient mice
AU - Kronenberg, Daniel
AU - Michel, Philipp A.
AU - Hochstrat, Eva
AU - Wei, Ma
AU - Brinckmann, Jürgen
AU - Müller, Marcus
AU - Frank, Andre
AU - Hansen, Uwe
AU - Eckes, Beate
AU - Stange, Richard
N1 - Funding Information:
Funding: This work was funded by the Deutsche Forschungsgemeinschaft through the Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster, Germany (to D.K. and R.S.) and CRC829 and FOR2722 (to B.E.)
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/2
Y1 - 2020/4/2
N2 - 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 α2β1 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 α2β1 deficiency. Tenocytes lacking integrin α2β1 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 α2β1 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 α2β1-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 α2β1 on collagen modifications in tendons. Its role in tendon pathologies, like chronic degradation, will be the subject of future investigations.
AB - 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 α2β1 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 α2β1 deficiency. Tenocytes lacking integrin α2β1 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 α2β1 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 α2β1-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 α2β1 on collagen modifications in tendons. Its role in tendon pathologies, like chronic degradation, will be the subject of future investigations.
UR - http://www.scopus.com/inward/record.url?scp=85083696097&partnerID=8YFLogxK
U2 - 10.3390/ijms21082835
DO - 10.3390/ijms21082835
M3 - Journal articles
C2 - 32325713
AN - SCOPUS:85083696097
SN - 1661-6596
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 8
M1 - 2835
ER -
