Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis

Abstract

BackgroundResearch suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear.MethodsWe harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence [K/L] grade 2–4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF.ResultsVEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle.ConclusionSynovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.

Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain

“…VEGF is a mediator of the angiogenic process, essential in the onset and development of joint inflammatory disorders including OA. In fact, it promotes tissue damage and pain both sustaining and increasing the invasion of inflammatory cells and local pain receptors, respectively [118–120]. Moreover, according to genome wide studies, disease severity increases along with VEGF expression [121].…”

Painful Understanding of VEGF

“…In osteoarthritis (OA), anomalous VEGF expression in synovial fluids has been associated with higher pain scores (Takano et al, 2018 ) and worse prognosis. VEGF seems to mediate cartilage degeneration, bone and neurovascular invasion of articular cartilage, increased migration and/or activity of macrophages, fibroblasts, and neutrophils.…”

SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia

“…Clinical findings that VEGF-A contributes to pain are supported by observations that in osteoarthritis increased VEGF expression in synovial fluids has been associated with higher pain scores [ 55 ]. VEGF-A has been reported to enhance pain behaviors in normal, nerve-injured and diabetic animals [ 23 ; 58 ].…”