ABSTRACT
Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Here, we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism. BA inhibited osteoclast differentiation and strongly suppressed interleukin-1 (IL-1) production. BA inhibited osteoclast formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1 treatment. The reporter assay and the inhibitor study of IL-1 transcription suggested that BA inhibited nuclear factor-B and activator protein-1 by regulating IB kinase, extracellular signal regulated kinase and P38, resulting in the down-regulation of IL-1 expression. BA also promoted osteoblast differentiation. Furthermore, BA protected lipopolysaccharide- and ovariectomy-induced bone loss in mice, suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.
ABSTRACT
BACKGROUND: The human placenta is an important organ in the maintenance of pregnancy, having functions in maturation and differentiation until the end of pregnancy. The bcl-2 protein is a proto-oncogene that prevents apoptosis and maintains cell survival. However, the mechanism through which bcl-2 inhibits apoptosis is unclear. The aims of this study are to localize bcl-2 at the placenta and to determine whether the expression of bcl-2 in early normal pregnancy is different from that of a missed abortion. METHODS: Immunohistochemistry was performed for bcl-2 in formalin-fixed chorionic villi and decidual tissue collected from five early normal pregnancies and eleven missed abortions having histories of recurrent abortions during the first trimester. RESULTS: The bcl-2 protein was observed in the syncytiotrophoblasts of chorionic villi and decidua in both the normal pregnancy and the missed abortion, and the expression of bcl-2 significantly increased in the missed abortion group (p<0.05). CONCLUSION: The bcl-2 may be necessary to maintain pregnancy through modulating the survival of the syncytiotrophoblast and decidua without affecting cell proliferation, and the increased bcl-2 expression is presumed to be a reparative process to the increased apoptotic activity.