George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA 30332.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332.
J Biomech Eng. 2022 Jul 1;144(7). doi: 10.1115/1.4053749.
The lymphatic system has been proposed to play a crucial role in preventing the development and progression of osteoarthritis (OA). As OA develops and progresses, inflammatory cytokines and degradation by-products of joint tissues build up in the synovial fluid (SF) providing a feedback system to exacerbate disease. The lymphatic system plays a critical role in resolving inflammation and maintaining overall joint homeostasis; however, there is some evidence that the lymphatics can become dysfunctional during OA. We hypothesized that the functional mechanics of lymphatic vessels (LVs) draining the joint could be directly compromised due to factors within SF derived from osteoarthritis patients (OASF). Here, we utilized OASF and SF derived from healthy (non-OA) individuals (healthy SF (HSF)) to investigate potential effects of SF entering the draining lymph on migration of lymphatic endothelial cells (LECs) in vitro, and lymphatic contractile activity of rat femoral LVs (RFLVs) ex vivo. Dilutions of both OASF and HSF containing serum resulted in a similar LEC migratory response to the physiologically endothelial basal medium-treated LECs (endothelial basal medium containing serum) in vitro. Ex vivo, OASF and HSF treatments were administered within the lumen of isolated LVs under controlled pressures. OASF treatment transiently enhanced the RFLVs tonic contractions while phasic contractions were significantly reduced after 1 h of treatment and complete ceased after overnight treatment. HSF treatment on the other hand displayed a gradual decrease in lymphatic contractile activity (both tonic and phasic contractions). The observed variations after SF treatments suggest that the pump function of lymphatic vessel draining the joint could be directly compromised in OA and thus might present a new therapeutic target.
淋巴系统被认为在预防骨关节炎（OA）的发生和发展中起着至关重要的作用。随着 OA 的发展和进展，炎症细胞因子和关节组织的降解产物在滑液（SF）中积聚，为疾病的恶化提供了反馈系统。淋巴系统在解决炎症和维持整体关节内稳态方面起着至关重要的作用；然而，有证据表明，在 OA 期间，淋巴管可能会出现功能障碍。我们假设，由于来自 OA 患者（OASF）的 SF 中的因素，引流关节的淋巴管（LV）的功能力学可能会直接受到损害。在这里，我们利用 OASF 和来自健康（非 OA）个体的 SF（健康 SF（HSF））来研究 SF 进入引流淋巴对体外淋巴管内皮细胞（LEC）迁移的潜在影响，以及离体大鼠股骨 LV（RFLV）的淋巴收缩活性。OASF 和 HSF 的血清稀释液在体外导致类似于生理内皮基础培养基处理的 LEC（含血清的内皮基础培养基）的 LEC 迁移反应。在离体状态下，在受控压力下将 OASF 和 HSF 处理物施用于分离的 LV 管腔内。OASF 处理短暂增强了 RFLV 的紧张性收缩，而 1 小时后，相位收缩显著减少，处理过夜后完全停止。另一方面，HSF 处理显示出淋巴收缩活性（紧张性和相位收缩）逐渐降低。SF 处理后的这些变化表明，OA 中引流关节的淋巴管的泵功能可能会直接受损，因此可能成为一个新的治疗靶点。
