Study On The Impact Of Celecoxib On Proliferation Of Human Osteoblasts

Background & Objective Various kinds of nonsteroidal anti-inflammatory drugs(NSAIDs) have been used in animals and human beings as analgesic agents for pain management in the treatment of orthopedic diseases, including osteoarthritis and fracture.The rapeutic effects of NSAIDs can be evoked by inhibiting the enzyme activity of cyclooxygenase(COX), resulting in decreased synthesis of inducible prostaglandin PGE2,which is one of key mediators of inflammation and a stimulator of pain-sensitizing neurons.Cyclooxygenase(COX), is a key enzyme in PG biosynthesis.PGE2 in osteogenesis is to promote differentiation and function of osteoblasts.Synthesis of PGE2 is a harmonized process of several enzymes,such as prostaglandin H2 synthases, including COX-1 and COX-2, and prostaglandin E synthases, consisting of cytosolic prostaglandin synthase(c PGES), microsomal prostaglandin synthase(m PGES)-1 and m PGES-2. In general, COX-1 is ubiquitous in most of cells for maintaining homeostasis, but COX-2 is an inducible enzyme that can be upregulated by various proinflammatory stimulus [35], and cyclooxygenase(COX) is a key enzyme in PG biosynthesis.m PGES-1 is induced coordinately with the COX-2 enzyme that can be upregulated by various proinflammatory stimuli.The aim of our study was to study on the impact of celecoxib on proliferation of human osteoblasts by targeting m PGES-1 and COX-2.Methods The human osteoblasts were cultured and divided three groups,including the negative control, positive control( stimulated by IL-1) and intervention group(celecoxib + IL-l),the detection of m RNA and protein level of COX-2 and m PGES-1 were measured by real tmie PCR(RT-PCR) and Western blot.MTT assay was performed to determine the impact of celecoxib on proliferation ofhuman osteoblasts which were treated with IL-1.Results RT-PCR and Western blot showed that the detection of m RNA and protein level of COX-2 and m PGES-1 of the positive control( stimulated by IL-1) were significantly higher than that of the negative control and intervention group(celecoxib + IL-l).Celecoxib had cytotoxic effect on the growth of osteoblasts, manifests dose dependence as well as increasing cell inhibition over time.Conclusion celecoxib could inhibit proliferation of osteoblasts, and could inhibit the occurrence of heterotopic ossification by regulating the level of m PGES-1 and COX-2 m RNA and protein.