Inflammatory cytokines via up-regulation of aquaporins deteriorated the pathogenesis of early osteoarthritis

Abstract

Background Inflammatory cytokines enhanced the progress of the pathogenesis of osteoarthritis, however the mechanisms remain unclear. The objective is to determine aquaporins (AQPs) in the pathogenesis of osteoarthritis. Methods and findings Primary rat articular chondrocytes were treated with IL-1β to mimic the early stage of osteoarthritis in vitro. Early osteoarthritis animal model was established by intra-articular injection of 4% papain. Micro- or ultra-structure histopathologic changes, cell viability, apoptosis cells and cell membrane permeability, locations and expressions of AQP1 and AQP3 and matrix were detected in the cartilage or in the chondrocytes of knee. IL-1β could reduce the chondrocytes viability, increase the apoptosis cells, and also impair the cell membrane and organelles. IL-1β significantly induced the up-regulation of AQP1 and AQP3 in the chondrocytes. In the chondrocytes, AQPs were mainly clustered in both membrane and perinuclear region of cytoplasm, while higher AQPs were detected in the superficial and middle layers of the cartilage. With the up-regulation of AQPs, the cartilage matrix was considerably decreased in both the chondrocytes and in the osteoarthritis cartilage. In the early osteoarthritis rat model, serum and synovial fluid confirmed that higher IL-1β could increase the expressions of AQPs, and decrease the cartilage matrix in both the chondrocytes and the cartilage. Conclusions Inflammatory cytokine IL-1β via up-regulation of AQPs caused the abnormal metabolism of water transport and loss of the cartilage matrix in the chondrocytes, and ultimately exacerbated the pathogenesis of early osteoarthritis. Therefore, AQPs may be a candidate therapeutic target for prevention and treatment of osteoarthritis.

lncRNA SNHG16 promotes the occurrence of osteoarthritis by sponging miR‑373‑3p

“…In addition, a recent study reported that the inflammatory response may have an important role during the progression of OA ( 22 ). Tan et al ( 23 ) indicated that the expression levels of IL-1β were increased in OA tissues. Furthermore, IL-1β promoted damage in arthritic cartilage and enhanced the expression levels of matrix-degradation proteins ( 24 ).…”

Total Flavonoids of Rhizoma Drynariae Restore the MMP/TIMP Balance in Models of Osteoarthritis by Inhibiting the Activation of the NF- κ B and PI3K/AKT Pathways

“…e proinflammatory cytokine interleukin-1β (IL-1β) can be produced by a series of cells, such as chondrocytes and synovial cells [8]. IL-1β can also significantly upregulate MMPs expression in chondrocytes, which has a critical effect on the progression of OA, especially in the early stage [9]. OA causes severe damage; however, effective and safe drugs to treat OA are still lacking [10].…”

Characterization of Early-Onset Finger Osteoarthritis-Like Condition Using Patient-Derived Induced Pluripotent Stem Cells

“…In the case of MMP13, day 21 efOA-CPs showed no expression in every trial. The use of AQP1 as a marker for OA, as suggested in several previous studies, remains controversial [13,14]. We observed that AQP1 expression in efOA-CPs increased significantly after chondrogenic differentiation (Figure 2j).…”