Takano Shotaro, Uchida Kentaro, Inoue Gen, Matsumoto Toshihide, Aikawa Jun, Iwase Dai, Mukai Manabu, Miyagi Masayuki, Takaso Masashi
Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, 252-0374, Japan.
Department of Pathology, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, 252-0374, Japan.
BMC Musculoskelet Disord. 2018 Jun 26;19(1):204. doi: 10.1186/s12891-018-2127-2.
Research 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.
We 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.
VEGF 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.
Synovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.
研究表明，膝关节骨关节炎（KOA）患者滑液中的血管内皮生长因子（VEGF）水平与KOA严重程度呈正相关。人类KOA患者滑液VEGF水平与疼痛之间的关系尚未完全明确，VEGF在疼痛通路中的作用仍不清楚。
我们在全膝关节置换术中从102例有KOA影像学证据（单侧Kellgren/Lawrence [K/L] 2-4级）的患者中获取滑膜（SM）。患者使用0至10厘米视觉模拟量表（VAS）对疼痛进行评分。比较了疼痛强烈/严重（VAS≥6）和轻度/中度疼痛（VAS<6）的KOA患者SM中VEGF水平。研究了VAS与VEGF mRNA表达之间的相关性。为了研究VEGF诱导疼痛的可能机制，通过免疫组织化学分析确定VEGF和神经肽apelin的分布。为了研究VEGF在调节apelin表达中的作用，将SM细胞暴露于VEGF。
VAS≥6组中VEGF的表达明显高于VAS<6组。VEGF的表达水平也与VAS呈正相关。在SM的衬里中鉴定出VEGF阳性细胞。与用载体处理的细胞相比，用外源性VEGF处理的SM细胞中apelin mRNA和蛋白的表达明显升高。
滑膜VEGF可能参与KOA的疼痛通路，其作用可能由apelin介导。
