This finding was also observed by Miyazaki et al.20 Changes in bone formation marker (OPG) were transient whilst changes in bone resorption markers (RANKL and TRAP) were constant. These results were confirmed by the immunohistochemistry of OPG protein, where the Selleck ABT 888 increase in the osteoblast cells was only

transient during the initial step of the alveolar wound healing in OVX rats (7 postoperative days), whilst the increase in the osteoclastic differentiation was constant throughout the experiment. Our findings suggest that raloxifene therapy reduces osteoblastic cells apoptosis and, probably, acts blocking the formation of osteoclasts brush borders more efficient than estradiol therapy. As the literature shows controversial Galunisertib cost findings,21, 22, 23, 24, 25, 26, 27 and 28 this findings are less discussed maybe due to the limited number of scientific papers that compare both therapies. Studies has shown that raloxifene therapy, in a dose dependent manner,

protects bone tissue blocking osteoclastogenesis, mature osteoclasts activation and their survival.27 and 29 Our findings indicate that raloxifene therapy compensates OVX statement by reducing the number of pre-osteoclasts and mature osteoclasts. As showed in this study in which OVX/RLX group presented a minor TRAP labelling at 28 postoperative days and an absence of TRAP labelling at 42 postoperative days compared to sham and OVX/E2 groups. Also we observed a minor RANKL expression on OVX/RLX group at 28 and 42 postoperative days compared to OVX/E2 group. The intense RANKL immunolabelling was more significant at 28 and 42 postoperative days on OVX group. This finding is in agreement to our previous studies in which we observed the least amount of bone formation at the same period

and same group.11 and 12 An important observation is the intense expression of RANKL and TRAP protein observed in some experimental groups emphasizing previous evidences4, 5, 19, 27, 28 and 29 that suggest the signalling role of the tumoural necrosis factor members (RANKL) on the osteoclastic responses (TRAP). Considering the signal cellular responses, raloxifene therapy decreased Anidulafungin (LY303366) RANKL immunolabelling and increased OPG immunolabelling, consequently decreasing TRAP. This finding is confirmed by previous studies4, 5, 19, 27, 28 and 29 that show the role of raloxifene therapy in protecting bone tissue that brings an important therapeutic option to keep bone tissue homeostasis. Studies of Cheung et al.30 in bone marrow cloned cells cultures (HCC1) with osteoblastic characteristics and primary human osteoblasts (HOB) showed a significant reduction in RANKL expression in cells treated with raloxifene whilst oestrogen treatment did not show significant changes. As RANKL/OPG balance showed a reduction on OVX/RLX group compared to OVX/E2 group. Another important finding of our study in which raloxifene acts is increasing OPG expression. A result also observed by Viereck et al.