Vaccaria hypaphorine impairs RANKL-induced osteoclastogenesis by inhibition of ERK, p38, JNK and NF-κB pathway and prevents inflammatory bone loss in mice - 31/12/17
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Abstract |
Osteoclasts are sole bone-resorbing cells which exert a profound effect on skeletal metabolism. The search for medicines that affect the differentiation and function of osteoclasts is crucial in developing therapies for osteoclast-based diseases. Vaccaria hypaphorine, the main active compound of the traditionally used Chinese herb Vaccaria segetalis, has anti-inflammatory activity. The present study demonstrated for the first time that vaccaria hypaphorine could significantly inhibit the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastic differentiation in vitro and alleviate lipopolysaccharide (LPS)-induced bone loss in vivo. Further study showed that vaccaria hypaphorine decreased osteoclastogenesis in a dose-dependent manner. Furthermore, vaccaria hypaphorine was confirmed to inhibit osteoclasts differentiation at early stage but not at later stage. Pit formation assay and F-actin ring staining showed that vaccaria hypaphorine inhibited the bone-resorbing activity of osteoclasts. Mechanistically, vaccaria hypaphorine impaired RANKL-induced osteoclastogenesis through reduction of extracellular signal-regulated kinases (ERK), p38, c-Jun N-terminal kinase (JNK) and NF-κB p65 phosphorylation. Taken together, our results provided evidences that vaccaria hypaphorine might be considered as potential therapeutic agent for treating osteoclast-based bone loss.
Le texte complet de cet article est disponible en PDF.Keywords : Osteoclast differentiation, Bone resorption, vaccaria hypaphorine, RAW264.7 cells.
Abbreviations : RANKL, LPS, ERK, JNK, M-CSF, MMP, TRAF, BMMs, MAPK, TNF, IL, α-MEM, FBS, CCK-8, OIM, Dex, TRAP, BMD, Tb.N, BV/TV, OD, TBST, EdU
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Vol 97
P. 1155-1163 - janvier 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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