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Figure 1 | Arthritis Research & Therapy

Figure 1

From: Celecoxib: considerations regarding its potential disease-modifying properties in osteoarthritis

Figure 1

Schematic representation of the in vitro effects of celecoxib (CBX) on cartilage degeneration. Cyclooxygenase (COX)-2 expression in the chondrocyte is induced by inflammatory mediators such as IL-1β and TNF-α (1). Subsequently, the prostanoid receptor EP4 is up-regulated via a COX-2-dependent mechanism (2). Increased COX-2 activity results in large concentrations of prostaglandin E2 (PGE2) (3). PGE2 exerts its effects through the prostanoid receptor EP4 (4), resulting in the increased expression of matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin repeats (ADAMTS)-5. Furthermore, PGE2 augments the release of newly formed proteoglycans from cartilage and reduces the synthesis of proteoglycans (5). IL-1β and TNF-α also activate the transcription factors NF-κB and JNK (6), which stimulate the expression of inducible nitric oxide synthase (iNOS) (7), resulting in the formation of nitric oxide (NO) (8). NO has a potential role in inducing chondrocyte apoptosis, inhibiting proteoglycan synthesis and stimulating MMP activity (9). Together, the effects of NO and PGE2 result in cartilage degeneration. Celecoxib prevents the negative effects of PGE2 and NO on cartilage destruction by inhibiting both COX-2 and NF-κB/JNK, thereby potentially slowing cartilage degradation in osteoarthritis.

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