title: Apoptosis of human primary osteoclasts treated with molecules targeting nuclear factor-kappaB.
abstract: Osteoclasts (OCs) are involved in several pathologies associated with bone loss, including rheumatoid arthritis, osteoporosis, bone metastasis of myeloma, osteosarcoma, and breast cancer. In this review we determined the effects of natural compounds, including extracts from medicinal plants, on differentiation and survival of human primary OCs obtained from peripheral blood. We found that OCs from umbilical cord blood and peripheral blood behave differently in response to molecules inducing apoptosis in this experimental system. Apoptosis induced by decoy oligonucleotides was reproducibly obtained in OCs from peripheral blood but not in OCs derived from cord blood. With respect to effects of medicinal plants, we found that crude extracts of Emblica officinalis are able to induce specifically programmed cell death of mature OCs without altering the process of osteoclastogenesis. E. officinalis specifically increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments BioPharmaNet demonstrate that E. officinalis extracts specifically compete with the binding of a transcription factor involved in osteoclastogenesis NF-kappaB to its specific target DNA sequences. This might explain the observed effects of E. officinalis on the expression levels of IL-6, an NF-kappaB-specific target gene. We suggest the application of natural products as an alternative tool for therapy applied to bone diseases.
authors.affiliation: BioPharmaNet, Department of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Piva
authors.forename: Letizia
authors.initials: L
authors.lastname: Penolazzi
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Lambertini
authors.forename: Elena
authors.initials: E
authors.lastname: Torreggiani
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D029842:Phyllanthus emblica / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D019014:fas Receptor; D004247:DNA