Open AccessAminothiazoles inhibit osteoclastogenesis and PGE 2 production in LPS ‐stimulated co‐cultures of periodontal ligament and RAW 264.7 cells, and RANKL ‐mediated osteoclastogenesis and bone resorption in PBMC s
Author(s) -
Kats Anna,
Gerasimcik Natalija,
Näreoja Tuomas,
Nederberg Jonas,
Grenlöv Simon,
Lagnöhed Ekaterina,
Desai Suchita,
Andersson Göran,
YucelLindberg Tülay
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14015
Subject(s) - rankl , osteoclast , chemistry , bone resorption , peripheral blood mononuclear cell , resorption , osteoprotegerin , prostaglandin e2 , prostaglandin e , endocrinology , medicine , microbiology and biotechnology , biochemistry , biology , in vitro , receptor , activator (genetics)
Inflammatory mediator prostaglandin E 2 ( PGE 2 ) contributes to bone resorption in several inflammatory conditions including periodontitis. The terminal enzyme, microsomal prostaglandin E synthase‐1 ( mPGES ‐1) regulating PGE 2 synthesis is a promising therapeutic target to reduce inflammatory bone loss. The aim of this study was to investigate effects of mPGES ‐1 inhibitors, aminothiazoles TH ‐848 and TH ‐644, on PGE 2 production and osteoclastogenesis in co‐cultures of periodontal ligament ( PDL ) and osteoclast progenitor cells RAW 264.7, stimulated by lipopolysaccharide ( LPS ), and bone resorption in RANKL ‐mediated peripheral blood mononuclear cells ( PBMC s). PDL and RAW 264.7 cells were cultured separately or co‐cultured and treated with LPS alone or in combination with aminothiazoles. Multinucleated cells stained positively for tartrate‐resistant acid phosphatase ( TRAP ) were scored as osteoclast‐like cells. Levels of PGE 2 , osteoprotegerin ( OPG ) and interleukin‐6, as well as mRNA expression of mPGES ‐1, OPG and RANKL were analysed in PDL cells. PBMC s were treated with RANKL alone or in combination with aminothiazoles. TRAP ‐positive multinucleated cells were analysed and bone resorption was measured by the CTX ‐I assay. Aminothiazoles reduced LPS ‐stimulated osteoclast‐like cell formation both in co‐cultures and in RAW 264.7 cells. Additionally, aminothiazoles inhibited PGE 2 production in LPS ‐stimulated cultures, but did not affect LPS ‐induced mPGES ‐1, OPG or RANKL mRNA expression in PDL cells. In PBMC s, inhibitors decreased both osteoclast differentiation and bone resorption. In conclusion, aminothiazoles reduced the formation of osteoclast‐like cells and decreased the production of PGE 2 in co‐cultures as well as single‐cell cultures. Furthermore, these compounds inhibited RANKL ‐induced bone resorption and differentiation of PBMC s, suggesting these inhibitors for future treatment of inflammatory bone loss such as periodontitis.