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Background  Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of  Emblica officinalis  fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.    Methods  The effects of extracts from  Emblica officinalis  on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of  Emblica officinalis  extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally,  in vitro  effects of  Emblica officinalis  extracts on NF-kB transcription factor activity were determined by gel shift experiments.    Results  Extracts of  Emblica officinalis  were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis.  Emblica officinalis  increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that  Emblica officinalis  extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that  Emblica officinalis  extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of  Emblica officinalis  on the expression levels of interleukin-6, a NF-kB specific target gene.    Conclusion  Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of  Emblica officinalis  extracts as an alternative tool for therapy applied to bone diseases.

Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis