title: Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: BioPharmaNet, ER-GenTech, Department of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy. pnlmlt@unife.it
authors.forename: Letizia
authors.initials: L
authors.lastname: Penolazzi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Mahmud Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.forename: Margherita
authors.initials: M
authors.lastname: Zennaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Piva
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D004268:DNA-Binding Proteins / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects*; D029842:Phyllanthus emblica; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D010936:Plant Extracts