The expression of vascular endothelial growth factor and Syndecan-4 in cartilage from osteoarthritic knees

Abstract

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors. Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren-Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Contribution of biomechanical forces to inflammation‐induced bone resorption

“…VEGF has been considered to play a role in osteoarthritis pathogenesis (Oh et al. ) and in cartilage pathologies (Beckmann et al. ), suggesting that our results could be extrapolated to other clinical situations involving inflammatory reactions.…”

MMP-9 mediated Syndecan-4 shedding correlates with osteoarthritis severity

“…Sdc4 has been shown to be crucially involved in OA pathogenesis, since Sdc4 ko mice are protected from disease induction 3 . Further, the upregulation of Sdc4 expression in OA cartilage has been shown 21 Additionally Sdc4 can be found in cartilage during the OA onset and was described to be upregulated under inflammatory conditions by the transcription factor NF-kB 1,6,22 . The shedding of Sdc4 is a constitutive process, which is upregulated during inflammation as well as under pathological conditions 10,23 .…”

Local intra‑articular injection of vascular endothelial growth factor accelerates articular cartilage degeneration in rat osteoarthritis model

“…Increases in MMP-3 and MMP-9 expression levels have been reported to be related with decreasedTIMP-1 and TIMP-2 ( 9 ). The role of VEGF in articular cartilage destruction has been confirmed by various studies, which, induces ADAMTS-4 ( 15 ), ADAMTS-5 ( 34 ) and MMPs expressions ( 32 ) in return, and degrades major ECM molecules, such as type II collagen ( 24 ), aggrecan ( 22 ). Type III collagen, TGF-β1 and ADMS-12 have been associated with synovial fibrosis in OA knees ( 15 ).…”