The splice variants VEGF(121) and VEGF(189) of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage

Objective. Vascular endothelial growth factor (VEGF) has recently been show n to play an important role during endochondral bone formation in hypertrop hic cartilage remodeling, ossification, and angiogenesis, but it is not exp ressed in normal adult cartilage. Since genes expressed during development often reappear in the disease state, we investigated whether VEGF and its r eceptors (VEGFRs) are expressed in osteoarthritic (OA) cartilage. Methods. VEGF production in OA cartilage from the tibial plateau was measur ed by enzyme-linked immunosorbent assay. Deposition of VEGF and VEGFR was d etermined by immunohistochemistry. Expression of messenger RNA for the diff erent VEGF splice forms and for VEGFR was analyzed by reverse transcriptase -polymerase chain reaction (RT-PCR). Results. Increased VEGF concentrations were measured in OA cartilage from t he tibial plateau, while VEGF was almost undetectable in normal cartilage b ut could be immunostained within the intracellular and pericellular matrice s of OA chondrocytes. In analyses of cartilage samples from all 10 OA patie nts evaluated, VEGF(121) and VEGF(189) were identified as the only VEGF spl ice forms expressed. RT-PCR and immunohistochemistry for VEGF in normal hya line cartilage yielded negative findings. In addition to VEGF, VEGFR-2 (kin ase domain region/fetal liver kinase 1), but not VEGFR-1 (fms-like tyrosine kinase 1), could be detected by RT-PCR in OA cartilage and immunostained o n OA chondrocytes. Conclusion. Apart from its production in hypertropbic chondrocytes, VEGF is also produced in chondrocytes of OA cartilage. While the splice variant VE GF(189) binds to extracellular matrix proteoglycans, VEGF(121) is diffused freely. Both proteins should contribute to the inflammatory process by auto crine/paracrine stimulation of chondrocytes, chemotaxis of macrophages, and promotion of angiogenesis.