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Int. J. Mol. Sci. 2014, 15(9), 15456-15474; doi:10.3390/ijms150915456

Mechanical Forces Induce Changes in VEGF and VEGFR-1/sFlt-1 Expression in Human Chondrocytes

1
Department of Anatomy and Cell Biology, Rheinisch–Westfälische Technische Hochschule (RWTH) Aachen University, 52074 Aachen, Germany
2
Institute of Experimental Musculoskeletal Medicine, University Muenster, 48149 Muenster, Germany
3
Department of Orthopaedic Surgery, RWTH Aachen University, 52074 Aachen, Germany
4
Department of Pathology, RWTH Aachen University, 52074 Aachen, Germany
5
Research Division, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY 10021, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 30 June 2014 / Revised: 22 August 2014 / Accepted: 25 August 2014 / Published: 1 September 2014
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
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Abstract

Expression of the pro-angiogenic vascular endothelial growth factor (VEGF) stimulates angiogenesis and correlates with the progression of osteoarthritis. Mechanical joint loading seems to contribute to this cartilage pathology. Cyclic equibiaxial strains of 1% to 16% for 12 h, respectively, induced expression of VEGF in human chondrocytes dose- and frequency-dependently. Stretch-mediated VEGF induction was more prominent in the human chondrocyte cell line C-28/I2 than in primary articular chondrocytes. Twelve hours of 8% stretch induced VEGF expression to 175% of unstrained controls for at least 24 h post stretching, in promoter reporter and enzyme-linked immunosorbent assay (ELISA) studies. High affinity soluble VEGF-receptor, sVEGFR-1/sFlt-1 was less stretch-inducible than its ligand, VEGF-A, in these cells. ELISA assays demonstrated, for the first time, a stretch-mediated suppression of sVEGFR-1 secretion 24 h after stretching. Overall, strained chondrocytes activate their VEGF expression, but in contrast, strain appears to suppress the secretion of the major VEGF decoy receptor (sVEGFR-1/sFlt-1). The latter may deplete a biologically relevant feedback regulation to inhibit destructive angiogenesis in articular cartilage. Our data suggest that mechanical stretch can induce morphological changes in human chondrocytes in vitro. More importantly, it induces disturbed VEGF signaling, providing a molecular mechanism for a stress-induced increase in angiogenesis in cartilage pathologies. View Full-Text
Keywords: VEGF-A; VEGFR-1/FLT-1; sVEGFR-1/FLT-1; cyclic stretch; strain; human chondrocyte; C-28/I2 VEGF-A; VEGFR-1/FLT-1; sVEGFR-1/FLT-1; cyclic stretch; strain; human chondrocyte; C-28/I2
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Beckmann, R.; Houben, A.; Tohidnezhad, M.; Kweider, N.; Fragoulis, A.; Wruck, C.J.; Brandenburg, L.O.; Hermanns-Sachweh, B.; Goldring, M.B.; Pufe, T.; Jahr, H. Mechanical Forces Induce Changes in VEGF and VEGFR-1/sFlt-1 Expression in Human Chondrocytes. Int. J. Mol. Sci. 2014, 15, 15456-15474.

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