FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2117599170> ?p ?o ?g. }

• W2117599170 endingPage "613" @default.
• W2117599170 startingPage "601" @default.
• W2117599170 abstract "Recent studies have shown that the mevalonate pathway plays an important role in skeletal metabolism. Statins stimulate bone morphogenetic proteins-2 (BMP-2) production in osteoblasts, implicating a possible beneficial role for statins in promoting anabolic effects on bone. Here, we investigated the effects of a lipophilic simvastatin on osteoblast differentiation using mouse myoblast C2C12 cells, in the presence of tumor necrosis factor-α (TNF-α), an inflammatory cytokine that inhibits osteogenesis. The addition of TNF-α to C2C12 cells suppressed the BMP-2-induced expression of key osteoblastic markers including Runx2 and alkaline phosphatase (ALP) activity. Simvastatin had no independent effects on Runx2 and alkaline phosphatase activity; however, it reversed the suppressive effects of TNF-α. The ability of simvastatin to reverse TNF-α inhibition of BMP-induced Smad1,5,8 phosphorylation and Id-1 promoter activity suggests the involvement of Smad signaling pathway in simvastatin action. In addition, cDNA array analysis revealed that simvastatin increased expression levels of Smads in C2C12 cells exposed to TNF-α that also activated mitogen-activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), P38, and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Simvastatin potently suppressed TNF-α-induced phosphorylation of ERK1/2 and SAPK/JNK by inhibiting TNF-α-induced membrane localization of Ras and RhoA. Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) reversed the simvastatin effects on TNF-α-induced activation of Ras/Rho/MAPK pathways. FPP and GGPP also restored the simvastatin effects on TNF-α-induced suppression of Runx2 and ALP activity. In addition, simvastatin decreased the expression levels of TNF type-1 and -2 receptor mRNAs. Collectively, simvastatin supports BMP-induced osteoblast differentiation through antagonizing TNF-α-to-Ras/Rho/MAPK pathway and augmenting BMP-Smad signaling, suggesting a potential usage of statins to ameliorate inflammatory bone damage." @default.
• W2117599170 created "2016-06-24" @default.
• W2117599170 creator A5030695626 @default.
• W2117599170 creator A5039655833 @default.
• W2117599170 creator A5041765648 @default.
• W2117599170 creator A5061676448 @default.
• W2117599170 creator A5068885243 @default.
• W2117599170 creator A5069532250 @default.
• W2117599170 creator A5075868440 @default.
• W2117599170 creator A5076008613 @default.
• W2117599170 creator A5085516821 @default.
• W2117599170 date "2008-01-03" @default.
• W2117599170 modified "2023-09-27" @default.
• W2117599170 title "Simvastatin antagonizes tumor necrosis factor-α inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-activated protein kinase pathway" @default.
• W2117599170 cites W1559889536 @default.
• W2117599170 cites W1583699618 @default.
• W2117599170 cites W1605085939 @default.
• W2117599170 cites W1935346479 @default.
• W2117599170 cites W1968295892 @default.
• W2117599170 cites W1974650517 @default.
• W2117599170 cites W1975828859 @default.
• W2117599170 cites W1977553486 @default.
• W2117599170 cites W1981874801 @default.
• W2117599170 cites W1987247016 @default.
• W2117599170 cites W1990020335 @default.
• W2117599170 cites W1990260132 @default.
• W2117599170 cites W1994182510 @default.
• W2117599170 cites W1994596418 @default.
• W2117599170 cites W2002346836 @default.
• W2117599170 cites W2012459203 @default.
• W2117599170 cites W2020364703 @default.
• W2117599170 cites W2020504510 @default.
• W2117599170 cites W2021438186 @default.
• W2117599170 cites W2022036429 @default.
• W2117599170 cites W2025046506 @default.
• W2117599170 cites W2026515633 @default.
• W2117599170 cites W2031407959 @default.
• W2117599170 cites W2042087846 @default.
• W2117599170 cites W2042207784 @default.
• W2117599170 cites W2042292319 @default.
• W2117599170 cites W2043803017 @default.
• W2117599170 cites W2051405987 @default.
• W2117599170 cites W2052164212 @default.
• W2117599170 cites W2054646118 @default.
• W2117599170 cites W2056515822 @default.
• W2117599170 cites W2057336811 @default.
• W2117599170 cites W2057710785 @default.
• W2117599170 cites W2057767897 @default.
• W2117599170 cites W2059059445 @default.
• W2117599170 cites W2062989937 @default.
• W2117599170 cites W2067236087 @default.
• W2117599170 cites W2067282269 @default.
• W2117599170 cites W2069233373 @default.
• W2117599170 cites W2069681479 @default.
• W2117599170 cites W2071124826 @default.
• W2117599170 cites W2077779110 @default.
• W2117599170 cites W2091419870 @default.
• W2117599170 cites W2094835614 @default.
• W2117599170 cites W2097477185 @default.
• W2117599170 cites W2099671682 @default.
• W2117599170 cites W2100391645 @default.
• W2117599170 cites W2101840353 @default.
• W2117599170 cites W2104188913 @default.
• W2117599170 cites W2106691610 @default.
• W2117599170 cites W2121200936 @default.
• W2117599170 cites W2134714663 @default.
• W2117599170 cites W2145653235 @default.
• W2117599170 cites W2150565253 @default.
• W2117599170 cites W2151990509 @default.
• W2117599170 cites W2153347595 @default.
• W2117599170 cites W2155138852 @default.
• W2117599170 cites W2158707966 @default.
• W2117599170 cites W2166919582 @default.
• W2117599170 cites W2293758038 @default.
• W2117599170 cites W2487632304 @default.
• W2117599170 doi "https://doi.org/10.1677/joe-07-0532" @default.
• W2117599170 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18310456" @default.
• W2117599170 hasPublicationYear "2008" @default.
• W2117599170 type Work @default.
• W2117599170 sameAs 2117599170 @default.
• W2117599170 citedByCount "106" @default.
• W2117599170 countsByYear W21175991702012 @default.
• W2117599170 countsByYear W21175991702013 @default.
• W2117599170 countsByYear W21175991702014 @default.
• W2117599170 countsByYear W21175991702015 @default.
• W2117599170 countsByYear W21175991702016 @default.
• W2117599170 countsByYear W21175991702017 @default.
• W2117599170 countsByYear W21175991702018 @default.
• W2117599170 countsByYear W21175991702019 @default.
• W2117599170 countsByYear W21175991702020 @default.
• W2117599170 countsByYear W21175991702021 @default.
• W2117599170 countsByYear W21175991702022 @default.
• W2117599170 countsByYear W21175991702023 @default.
• W2117599170 crossrefType "journal-article" @default.
• W2117599170 hasAuthorship W2117599170A5030695626 @default.
• W2117599170 hasAuthorship W2117599170A5039655833 @default.
• W2117599170 hasAuthorship W2117599170A5041765648 @default.
• W2117599170 hasAuthorship W2117599170A5061676448 @default.

• next