The prevention of latanoprost on osteoclastgenesis in vitro and lipopolysaccharide‐induced murine calvaria osteolysis in vivo. Issue 6 (28th February 2018)

• Record Type: Journal Article
• Authors: Xu, Xing; Yan, Yufei; Liu, Zhuochao; Qi, Jin; Qian, Niandong; Zhou, Hanbing; Zhou, Qi; Wang, Tianqi; Huang, Ping; Guo, Lei; Jiang, Min; Deng, Lianfu
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 6(2018)
• Page Start: 4680
• Page End: 4691
• Publication Date: 2018-02-28
• Subjects: bone resorption -- latanoprost -- lipopolysaccharide‐induced murine calvaria osteolysis -- osteoclast; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26646
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Identification of agents that inhibit osteoclast formation and function is important for the treatment of osteolytic diseases which feature excessive osteoclast formation and bone resorption. Latanoprost (LTP), an analog of prostaglandin F2α, is a medication which works to lower pressure inside the eyes. Prostaglandin F2α was reported to regulate bone metabolism, however, the effect of LTP in osteoclastogenesis is still unknown. Here, we found that LTP suppressed RANKL‐induced osteoclastogenesis in a dose‐dependent manner as illustrated by TRAP activity and TRAP staining. In addition, the osteoclast function was also reduced by LTP treatment, as indicated in less osteoclastic resorption pit areas. Furthermore, LTP inhibited the mRNA expressions of osteoclast marker genes such as TRAP and cathepsin K. In order to illustrate its molecular mechanism, we examined the changing of mRNA and protein levels of NFATc1 and c‐fos by LTP treatment, as well as the phosphorylation of ERK, AKT, JNK, and p38. The results suggested that LTP inhibited RANKL‐induced osteoclastgenesis and function by inhibiting ERK, AKT, JNK, and p38 cascade, following by the c‐fos/NFATc1 pathway. In agreement with in vitro results, using an in vivo lipopolysaccharide‐induced murine calvaria osteolysis mouse model, we found that administration of LTP was able to reverse the lipopolysaccharide‐induced bone loss. Together, these data demonstrated that LTP attenuated the bone loss in lipopolysaccharide‐induced murine calvaria osteolysis mice through inhibiting osteoclast formation and function. Our study thus provided the evidences that LTP was a potential treatment option against osteolytic bone diseases. Abstract : Old drug latanoprost blocked osteoclastogenesis and bone resorption in vitro and in vivo as eveluated in LPS‐induced calvarial bone resorption. Latanoprost blocked osteoclast function through suppression of AKT, ERK, JNK, and p38 following by c‐fos/NFATc1 signaling pathway.