Bone Abstracts

Indoxyl sulfate (IS) is one of a number of protein-bound uremic toxins that accumulate in patients with chronic kidney disease. Current conventional hemodialysis is ineffective at removing this toxin. Although IS may impair osteoblast function and induce abnormalities of bone turnover or arthropathy, the effects on knee joint tissue by IS has not been investigated yet. The present studies have been carried out to test the IS effects on synovial fibroblasts, meniscal fibrochondrocytes, and articular chondrocytes.

Our results showed a significant upregulation of cyclooxygenase 2 (COX-2) and interleukin 8 (IL8) in three type cells following IS treatment at a concentration of 100 μg/ml for 24 h. COX-2 was increased 11.52±4.95, 4.21±0.89, and 3.95±0.35-fold in synovial fibroblasts, meniscal fibrochondrocytes, and articular chondrocytes respectively. IL8 showed 5.87±2.32, 2.98±1.00, and 2.31±0.93-fold increase in synovial fibroblasts, meniscal fibrochondrocytes, and articular chondrocytes respectively. A dose dependent manner was also identified. IL6 showed no significant change at the same condition examined. The production of nitric oxide (NO) by Griess reaction was 1.62±0.55 and 1.28±0.34-fold increase in synovial fibroblasts and meniscal fibrochondrocytes respectively.

Uremic toxins have been identified to metabolism by organic anion transporters (OATs) which the roles in joint tissue were unknown. The expression and regulation of OAT1, OAT2, OAT3, OAT4, and URAT1 in three type cells following IS stimulation was then examined. We here first identified that only OAT4, not OAT 1-3 and URAT1, was expressed in three type cells. The novel upregulation of OAT4 by IS stimulation was recognized and showed OAT4 1.83±0.47 and 2.46±0.93-fold increase in synovial fibroblasts and meniscal fibrochondrocytes respectively.

Our results showed that IS may induce inflammatory response and oxidative stress in synovial fibroblasts, meniscal fibrochondrocytes and articular chondrocytes. OAT4 may play an important role in IS metabolism in joint tissue.