血管生成和血管内皮生长因子(VEGF)参与骨关节炎(OA)。我们先前报道了贝伐单抗在兔OA模型中的抑制作用。在目前的研究中,我们调查了lenvatinib的效果,一种靶向VEGF和成纤维细胞生长因子受体的血管生成抑制剂,关于滑膜炎,骨赘形成,和兔OA模型中的软骨变性。创伤后OA是通过每只兔的一个膝盖上的前交叉韧带横断(ACLT)引起的。根据以下lenvatinib剂量将兔分为四组:未治疗的对照组(n=12),L0.3:0.3mg/kg/天(n=15),L1.0:1.0mg/kg/天(n=14),和L3.0:3.0mg/kg/天(n=13)组。我们使用无电容测试仪测量的体重分布比评估肢体疼痛,宏观骨赘形成,股骨髁滑膜和软骨组织学。对于软骨评估,分别评估了以下股骨远端部位:股骨胫骨(FT),股髌骨(FP),和股骨角(FP和FT之间)。L0.3和L1.0组术后12周时的体重分配率高于对照组。L0.3,L1.0和L3.0组的骨赘形成和滑膜炎评分明显低于对照组。英国《金融时报》骨关节炎研究学会国际评分,角落,L0.3组的FP位点低于对照组。L0.3组的FT和角落部位的软骨厚度比明显低于对照组。Krenn的软骨滑膜炎分级系统显示,所有lenvatinib给药组的评分均明显低于对照组。L3.0组软骨组织中MMP3的表达程度显著低于其他三组。与对照组和L0.3组相比,L3.0组的ADAMTS5表达较低。口服乐伐替尼抑制滑膜炎,骨赘形成,在兔ACLT模型中软骨退化和疼痛减轻。Lenvatinib是一种口服VEGF抑制剂,比其他VEGF抑制剂更容易给药,并且可能具有治疗创伤后OA的潜力。
Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis,
osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic
osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group.
Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn\'s grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis,
osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.