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• W2508619429 abstract "Approaches of targeting excessive activation and differentiation of osteoclasts were considered as an effective treatment option for osteoporosis or osteopenia. In the present work, a series of rhein derivatives were synthesized and employed for their cytotoxicity screening against bone marrow-derived macrophages cells (BMMs) and their inhibition effects on osteoclasts activation and differentiation in vitro using an MTT assay and a TRAP activity assay respectively. Two rhein derivatives d6 and d11 inhibited BMMs activation and differentiation with 98% and 85% inhibitory activity respectively, without showing any cytotoxicity on BMMs. Subsequently, the most potent compound d6 was further validated for its inhibitory effects on the formation of TRAP-positive multinucleated cells and bone resorption as evaluated by TRAP staining and bone resorption assay. The regulation by d6 of osteoclast marker genes assay revealed that treatment of BMMs with M-CSF and RANKL resulted in the stimulation of mRNA expressions of NFATc1, c-fos, TRAP, MMP-9 and cathepsin K which were highly related with osteoclast activation and differentiation, while d6 decreased mRNA expressions of these genes. It was indicated that d6 might regulate osteoclasts activity through RANKL/RANK/NFATc1 pathway. Thus our current work is expected to provide a highly promising approach for the development of a new type of anti-osteoporosis agent." @default.
• W2508619429 created "2016-09-16" @default.
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• W2508619429 date "2016-11-01" @default.
• W2508619429 modified "2023-10-17" @default.
• W2508619429 title "Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption" @default.
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• W2508619429 doi "https://doi.org/10.1016/j.ejmech.2016.08.004" @default.
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