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Mechanical forces induce changes in VEGF and VEGFR-1/sFlt-1 expression in human chondrocytes.

Beckmann R, Houben A, Tohidnezhad M, Kweider N, Fragoulis A, Wruck CJ, Brandenburg LO, Hermanns-Sachweh B, Goldring MB, Pufe T, Jahr H - Int J Mol Sci (2014)

Bottom Line: 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).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 Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, 52074 Aachen, Germany. rbeckmann@ukaachen.de.

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.

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Morphological changes in stretched chondrocytes. C-28/I2 cells were stretched (8%) for 12 h using cyclic square waveforms at 0.5 Hz and immediately fixed on the silicone membrane. Shown are representative scanning electron micrographs of unstrained cells (strain ctrl: A,C) and stretched cells (strain: B,D). Scale bars represent 25 μm. n = 3.
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ijms-15-15456-f007: Morphological changes in stretched chondrocytes. C-28/I2 cells were stretched (8%) for 12 h using cyclic square waveforms at 0.5 Hz and immediately fixed on the silicone membrane. Shown are representative scanning electron micrographs of unstrained cells (strain ctrl: A,C) and stretched cells (strain: B,D). Scale bars represent 25 μm. n = 3.

Mentions: Using scanning electron microscopy (SEM), we confirmed the typical polygonal morphology of C-28/I2 cells. Strained cells (Figure 7B,D) showed a more prominently pronounced nucleus as compared to non-stretched cells (Figure 7A,C). In addition, they revealed a higher averaged nucleus/cytoplasm ratio as the cytoplasm of strained cells appeared more condensed and cells revealed characteristic knot-like condensations at the cellular periphery (Figure 7D). The latter could be caused by adhesive structures. Furthermore, the cellular protrusions (i.e., filopodia) appear more directed, possibly aligned in the direction of the strain. Stretched cells also reveal characteristic knot-like condensations at the cellular periphery (Figure 7D).


Mechanical forces induce changes in VEGF and VEGFR-1/sFlt-1 expression in human chondrocytes.

Beckmann R, Houben A, Tohidnezhad M, Kweider N, Fragoulis A, Wruck CJ, Brandenburg LO, Hermanns-Sachweh B, Goldring MB, Pufe T, Jahr H - Int J Mol Sci (2014)

Morphological changes in stretched chondrocytes. C-28/I2 cells were stretched (8%) for 12 h using cyclic square waveforms at 0.5 Hz and immediately fixed on the silicone membrane. Shown are representative scanning electron micrographs of unstrained cells (strain ctrl: A,C) and stretched cells (strain: B,D). Scale bars represent 25 μm. n = 3.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4200847&req=5

ijms-15-15456-f007: Morphological changes in stretched chondrocytes. C-28/I2 cells were stretched (8%) for 12 h using cyclic square waveforms at 0.5 Hz and immediately fixed on the silicone membrane. Shown are representative scanning electron micrographs of unstrained cells (strain ctrl: A,C) and stretched cells (strain: B,D). Scale bars represent 25 μm. n = 3.
Mentions: Using scanning electron microscopy (SEM), we confirmed the typical polygonal morphology of C-28/I2 cells. Strained cells (Figure 7B,D) showed a more prominently pronounced nucleus as compared to non-stretched cells (Figure 7A,C). In addition, they revealed a higher averaged nucleus/cytoplasm ratio as the cytoplasm of strained cells appeared more condensed and cells revealed characteristic knot-like condensations at the cellular periphery (Figure 7D). The latter could be caused by adhesive structures. Furthermore, the cellular protrusions (i.e., filopodia) appear more directed, possibly aligned in the direction of the strain. Stretched cells also reveal characteristic knot-like condensations at the cellular periphery (Figure 7D).

Bottom Line: 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).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 Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, 52074 Aachen, Germany. rbeckmann@ukaachen.de.

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.

Show MeSH
Related in: MedlinePlus