LAUSR

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 joint homeostasis, however, there is 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 OA patients (OASF). Here, we utilized OASF and SF derived from healthy individuals (HSF) to investigate effects of SF entering the draining lymph on migration of lymphatic endothelial cells (LECs) in vitro, and lymphatic contractility of rat femoral LVs (RFLVs) ex vivo. Dilutions of OASF and HSF led to an increased migratory response in vitro compared to LECs treatment with media without serum. 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 hr of treatment and complete ceased after overnight treatment. HSF treatment on the other hand displayed a gradual decrease in lymphatic contractility (both tonic and phasic contractions). The observed variations after SF treatments suggest the pump function of LV draining the joint could be directly compromised in OA and thus might present a new therapeutic target.