Giuliani et al. reported that the anabolic effect of BPs was associated with the stimulation of b FGF, while Mundy et al. demonstrated that the anabolic effect of statins, which influence the mevalonate pathway as BPs, was due to their stimulation of Bone Morphogenetic Pro tein Crizotinib NSCLC 2, BMP 2 gene expression was also upregulated during osteoblast maturation after BP treat ment. Von Inhibitors,Modulators,Libraries Knoch et al. showed that a cascade of osteoblast related genes including BMP 2, cbfa 1, type 1 collagen and Bone Sialo Proteins were up regu lated and significantly increased in bone marrow stromal cells after BP treatment. The Osteoprotegerin Receptor Activator of Nuclear Factor B Ligand system is also influenced by BPs and may be related, at least in part, to the stimulatory effects of BPs on osteoblastic differentiation.

In addition, it has been shown that exogenous and endogenous prostaglandins modulate both bone Inhibitors,Modulators,Libraries formation and resorption. PGs are produced by cyclooxygenase, which is a rate limiting enzyme that converts arachidonic acid to PGs. Three iso forms of COX are recognized, COX 1, which is consti tutively expressed, COX 2, which is inducible by multiple factors and involved in PGs production Inhibitors,Modulators,Libraries during inflammation and other acute responses and COX 3, which has recently been related to paracetamol induced hypothermia and analgesia. On the con trary, the inhibition of cyclooxygenase has been associated with decreased bone formation in vivo and delayed experimental fracture healing. Strontium ranelate, a new treatment for postmeno pausal osteoporosis that exerts both antiresorptive and anabolic effects on bone, is able to influence prosta glandins metabolism.

Strontium ranelate induces COX 2 expression and Inhibitors,Modulators,Libraries promotes PGE2 production and activity in murine primary calvarian osteoblast trough ERK pathway. It also increases osteoblastic differentiation and mineralization, acting on early osteoblastic precursors to induce COX 2 and PGE2 production. Up Inhibitors,Modulators,Libraries to now, http://www.selleckchem.com/products/Abiraterone.html studies about the effects of BPs on cyclooxygenase are lacking. On the basis of these data, we hypothesized that BPs could upregulate COX 2 expression according to their putative anabolic effect on bone previously suggested by histomorphometric results. To verify this hypothesis, we studied the effect of Ris by evaluating histomorphometric parameters in rat tibiae and apoptosis and COX 2 expression in femur speci mens in the presence or absence of a negative effect on osteoblastic osteocytic lineage induced by glucocorti coids. To verify the presence of a direct stimulus of Ris on osteoblastic cells, we analysed in vitro the viability and COX 2 gene expression in bone marrow stromal cells treated with Ris at different concentrations, in the presence and absence of NS 398, a selective COX 2 inhibitor.