Universität zu Köln

Tempfer, Herbert, Spitzer, Gabriel, Lehner, Christine, Wagner, Andrea, Gehwolf, Renate, Fierlbeck, Johann, Weissenbacher, Nadja, Jessen, Malik ORCID: 0000-0002-7845-2758, Heindl, Ludwig M. and Traweger, Andreas ORCID: 0000-0002-0220-4766 (2022). VEGF-D-mediated signaling in tendon cells is involved in degenerative processes. Faseb J., 36 (2). HOBOKEN: WILEY. ISSN 1530-6860

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Abstract

Vascular endothelial growth factor (VEGF) signaling is crucial for a large variety of cellular processes, not only related to angiogenesis but also in nonvascular cell types. We have previously shown that controlling angiogenesis by reducing VEGF-A signaling positively affects tendon healing. We now hypothesize that VEGF signaling in non-endothelial cells may contribute to tendon pathologies. By immunohistochemistry we show that VEGFR1, VEGFR2, and VEGFR3 are expressed in murine and human tendon cells in vivo. In a rat Achilles tendon defect model we show that VEGFR1, VEGFR3, and VEGF-D expression are increased after injury. On cultured rat tendon cells we show that VEGF-D stimulates cell proliferation in a dose-dependent manner; the specific VEGFR3 inhibitor SAR131675 reduces cell proliferation and cell migration. Furthermore, activation of VEGFR2 and -3 in tendon-derived cells affects the expression of mRNAs encoding extracellular matrix and matrix remodeling proteins. Using explant model systems, we provide evidence, that VEGFR3 inhibition prevents biomechanical deterioration in rat tail tendon fascicles cultured without load and attenuates matrix damage if exposed to dynamic overload in a bioreactor system. Together, these results suggest a strong role of tendon cell VEGF signaling in mediation of degenerative processes. These findings give novel insight into tendon cell biology and may pave the way for novel treatment options for degenerative tendon diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tempfer, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Spitzer, Gabriel UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehner, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehwolf, Renate UNSPECIFIED UNSPECIFIED UNSPECIFIED Fierlbeck, Johann UNSPECIFIED UNSPECIFIED UNSPECIFIED Weissenbacher, Nadja UNSPECIFIED UNSPECIFIED UNSPECIFIED Jessen, Malik UNSPECIFIED orcid.org/0000-0002-7845-2758 UNSPECIFIED Heindl, Ludwig M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Traweger, Andreas UNSPECIFIED orcid.org/0000-0002-0220-4766 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-673638
DOI:	10.1096/fj.202100773RRR
Journal or Publication Title:	Faseb J.
Volume:	36
Number:	2
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1530-6860
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; CYCLIC TENSILE STRAIN; EXPRESSION; INTERLEUKIN-1-BETA; CANCER Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67363