Figure 3.

Schematic representation of the main effects of celecoxib (CBX) on subchondral bone. IL-1β induces the expression of cyclooxygenase (COX)-2 in chondrocytes (1) and osteoblasts (2), leading to production of receptor activator of NF-κB ligand (RANKL). RANKL stimulates the differentiation of osteoclast precursor cells into quiescent osteoclasts (3). Furthermore, it induces the expression of COX-2 and prostaglandin E2 (PGE2) in quiescent osteoclasts, and subsequently PGE2 activates osteoclasts in both an autocrine and paracrine manner (4). Celecoxib inhibits the COX-2-dependent RANKL production by chondrocytes and osteoblasts, thereby avoiding osteoclastogenesis and osteoblast activity. Furthermore, celecoxib directly inhibits the differentiation of precursor cells, independent of RANKL production by stromal cells. Celecoxib can also directly affect the osteoclasts themselves by decreasing RANKL-induced PGE2 expression and inhibiting carbonic anhydrase. Decreased carbonic anhydrase activity will diminish acidification of the resorption pit, and hence decrease osteoclast activity (5).

Zweers et al. Arthritis Research & Therapy 2011 13:239   doi:10.1186/ar3437
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