Glutathione accelerates osteoclast differentiation and inflammatory bone destruction

Autor:	Mitsuaki Ono, Hideyo Ohuchi, Tetsuya Ogino, Eriko Aoyama, Yoichi Kondo, Hirofumi Fujita, Masahiko Ochi
Rok vydání:	2019
Předmět:	musculoskeletal diseases 0301 basic medicine Programmed cell death Lipopolysaccharide Osteoclasts Inflammation Biochemistry Bone resorption Mice 03 medical and health sciences chemistry.chemical_compound Osteoclast medicine Animals Buthionine sulfoximine Bone Resorption Osteitis 030102 biochemistry & molecular biology biology Cell Differentiation General Medicine Glutathione Cell biology 030104 developmental biology medicine.anatomical_structure chemistry RANKL biology.protein medicine.symptom
Zdroj:	Free Radical Research. 53:226-236
ISSN:	1029-2470 1071-5762
Popis:	Chronic inflammation associated with bone tissues often destructs bones, which is essentially performed by osteoclasts in the presence of immunoregulatory molecules. Hence, regulating osteoclastogenesis is crucial to develop therapeutics for bone-destructive inflammatory diseases. It is believed that reactive oxygen species (ROS) are involved in receptor activator of NF-κB (RANK) ligand (RANKL)-induced osteoclast differentiation, and, therefore, glutathione (GSH), the most abundant endogenous antioxidant, suppresses osteoclast differentiation and bone resorption by RANKL. Interestingly, GSH also contributes to inflammatory responses, and the effects of GSH on osteoclast differentiation and bone destruction under inflammatory conditions have not yet been determined. Here, we investigated how GSH affects inflammatory cytokine-stimulated osteoclast differentiation in vitro and in a mouse model of inflammatory bone destruction. We found that GSH significantly promoted TNFα-stimulated osteoclast formation, while an inhibitor of GSH synthesis, buthionine sulfoximine, suppressed it. GSH facilitated the nuclear localisation of the nuclear factor of activated T cells c1 (NFATc1) protein, a master regulator of osteoclastogenesis, as well as the expression of osteoclast marker genes in a dose-dependent manner. N-acetylcysteine, a substrate of GSH synthesis, also stimulated osteoclast formation and NFATc1 nuclear localisation. GSH did not suppress cell death after osteoclast differentiation. In mouse calvaria injected with lipopolysaccharide, GSH treatment resulted in a fivefold increase in the osteolytic lesion area. These results indicate that GSH accelerates osteoclast differentiation and inflammatory bone destruction, suggesting GSH appears to be an important molecule in the mechanisms responsible for inflammatory bone destruction by osteoclasts.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b81b84335d7864da388735a1defac72b https://doi.org/10.1080/10715762.2018.1563782 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.