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

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.

WITHDRAWN: Evaluation of clinical, pathological and genetic indicators in chickens with thiram-induced tibial dyschondroplasia

“…On other hand Herzog et al [29] stated that increased blood vessel formation was observed in TD in which the low level of Flk-1 was described as one of the rate-limiting factors of blood-vessel formation that resulted in the unvascularized growth plate. An in vitro model of human chondrocyte culture also showed an increase in the expression level of VEGF [30,31]. Thiram appeared to be effective in up-regulating VEGF expression, suggesting that thiram has proangiogenic activity [21].…”

Angiopoietin‐like 4 promotes angiogenesis in the tendon and is increased in cyclically loaded tendon fibroblasts

“… b ; Beckmann et al . ). TGF‐β isoforms and their receptors have broad biological functions and are involved in different processes in tendon tissue, including development, growth, healing, adaptation and tissue homeostasis (Fenwick et al .…”

Transcriptome-based screening of intracellular pathways and angiogenesis related genes at different stages of thiram induced tibial lesions in broiler chickens

“…Thiram is lipophilic in nature and combined with the cell membrane to cause cytotoxicity, bone formation disorder, cartilage cell damage and immune depressions. It can also cause membrane damage, bone morphogenic inactivation and inhibit angiogenesis [12,13]. In TD, a large number of the cartilage cell damage is due to the apoptosis process and abnormal protein secretion in the cartilage cells, causing a decrease in the cartilage extracellular matrix degradation rate, which limits the space for bone deposition [14,15].…”