Author/Editor     Mencej Bedrač, Simona; Marc, Janja
Title     Sistem Rankl/RANK/OPG - nova tarča za zdravila za zdravljenje osteoporoze
Translated title     RANKL/RANK/OPG system - new target for drugs for osteoporosis treatment
Type     članek
Vol. and No.     Letnik 59, št. 4
Publication year     2008
Volume     str. 175-178
ISSN     0014-8229 - Farmacevtski vestnik
Language     slv
Abstract     Raziskave kažejo, da je sistem RANKL/RANK/OPG pomembna nova tarča za zdravila za zdravljenje osteoporoze. Je eden od lokalnih dejavnikov, ki uravnava kostno remodelacijo oz. kostno razgradnjo. Vpliva na osteoklastogenezo, v kateri nastanejo zreli osteoklasti, in na aktivacijo zrelih osteoklastov. Po vezavi RANKL na receptor RANK se pospešijo procesi diferenciacije in aktivacije osteoklastov ter zlitja do več jedrnih osteoklastov, njihovo preživetje se podaljša, apoptoza osteoklastov pa je upočasnjena. To poveča razgradnjo kostnine, kar vodi do zmanjšanja kostne mase in bolezni npr. osteoporoze. Po drugi strani OPG z vezavo na RANKL prepreči učinke RANKL ter tako zmanjša razgradnjo kostnine in deluje v smeri povečanja kostne mase. Pri preučevanju možnosti terpevtske uporabe zdravilnih učinkovin z delovanjem na sistem RANKL/RANK/OPG sta se kot najboljša pozkazala fuzijski protein OPG-Fc in človeško monoklonsko protiteloproti RANKL - denosumab. Zaradi možnih tveganj pri uporabi fuzijskega protein OPG-Fc se je kot mnogo obetavnejša izkazala uporaba denosumaba.Data show that RANKL/RANK/OPG system is an important new target for drugs for osteoporosis treatment. It is one of the local factors that influence bone remodelling or bone resorption. Its primary influence is on the osteoclastogenesis, in which osteoclasts develop, and on mature osteoclast activation. Following RANKL binding to RANK receptor the osteoclast differentiation, activation and fusion are accelerated, their survival is prolonged and the apoptosis is decreased. Bone resorption is increased and followed by bone loss and development of diseases like osteoporosis. On the other hand, OPG binding to RANKL prevents RANKL effects and leads to decreasedbone resorption and increased bone mass. Therapeutic implications of active substances, influencing RANKL/RANK/OPG system, have also been studied and the best results were obtained from the use of OPG-Fc fusion protein and human monoclonal RANKL antibody denosumab. Due to possible risks with OPG-Fc fusion protein application, the use of denosumab is far more promising.
Keywords     RANKL
RANK
OPG
osteoporoza
denosumab