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

摘要

Background: Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated withbone loss. Recent results support the concept that some medicinal plants and derived natural products are ofgreat interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis andosteoporosis. In this study we determined whether extracts of Emblica officinalis fruits display activity of possibleinterest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of humanprimary osteoclasts.Methods: The effects of extracts from Emblica officinalis on differentiation and survival of human primary OCscultures 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 apoptosiswere studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, in vitro effectsof 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, withoutaltering, at the concentrations employed in our study, the process of osteoclastogenesis. Emblica officinalisincreased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experimentsdemonstrated that Emblica officinalis extracts act by interfering with NF-kB activity, a transcription factor involvedin osteoclast biology. The data obtained demonstrate that Emblica officinalis extracts selectively compete with thebinding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observedeffects 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 withrheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducingosteoporosis. Accordingly, we suggest the application of Emblica officinalis extracts as an alternative tool fortherapy applied to bone diseases.