Abstract
Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1β stimulated the expression of prostaglandin (PG) receptor EP4 via increased PGE2 production. However, the effect of IL-1β on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1β and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1β on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1β; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1β. Conditioned medium from IL-1β-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1β suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs.
Highlights
Bone remodeling in joints involves the synthesis of bone matrix by osteoblasts and its resorption by mature osteoclasts
Consistent with the results obtained for gene expression, RANKL protein expression was significantly higher in the presence of IL-1β compared to untreated control cells on days 21 and 28 (Figure 1(b))
We demonstrated that IL-1β increased the production of prostaglandin E2 (PGE2), COX-2, and PG receptor EP4 in human chondrocytes, suggesting that the IL-1β promotes the expression of EP4 by an autocrine mechanism involving increased PGE2 production in chondrocytes [23]
Summary
Bone remodeling in joints involves the synthesis of bone matrix by osteoblasts and its resorption by mature osteoclasts. Arthrosis of the TMJ is accompanied by symptoms such as pain and joint sound during jaw movement [11], and results from an imbalance between predominantly chondrocyte-controlled anabolic and catabolic processes It is characterized by the progressive degradation of components of the articular cartilage extracellular matrix and is associated with inflammatory factors [12,13,14]. Several studies [15,16,17,18] have found elevated levels of the cytokine IL-1β in synovial fluid samples obtained from TMJ patients with osteoarthritis, and elevated concentrations of IL-1β in synovial fluid have been implicated in joint cartilage destruction For these reasons, we attempted to clarify the effect of IL-1β on chondrocyte function. We examined the effects of IL-1β and celecoxib, a specific inhibitor of COX-2 [24, 25], on the expression of M-CSF, RANKL, and OPG in human chondrocytes, and the indirect effect of IL-1β on the formation of osteoclast-like cells using RAW264.7 cells as osteoclast precursors
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