Matches in SemOpenAlex for { <https://semopenalex.org/work/W4379259501> ?p ?o ?g. }
- W4379259501 endingPage "48" @default.
- W4379259501 startingPage "37" @default.
- W4379259501 abstract "Osteopenia and fragile fractures are diabetes-associated complications. Many hypoglycemic drugs have effects on bone metabolism. Metformin, as is a prescribed medication for type 2 diabetes mellitus (T2DM), had been reported to have osteoprotective effects beyond its hypoglycemic effect, however the potential mechanism behind these effects remains unclear. In this study, we aimed to investigate the comprehensive effects of metformin on bone metabolism in T2DM rat model and elucidate the potential mechanism. Goto-Kakizaki spontaneous T2DM rats with significant hyperglycemia were treated with/without metformin for 20 weeks. Glucose tolerance was tested and all rats were weighed every two weeks. The osteoprotective effects of metformin in diabetic rats were determined by quantifying serum bone biomarkers, μ-CT imaging, histological staining, bone histomorphometry, and biomechanical properties analyses. Potential targets of metformin in the treatment of T2DM and osteoporosis were predicted using network pharmacology. The effects of metformin on mesenchymal stem cells (C3H10) cultured in high glucose medium were evaluated by CCK-8 assay, alkaline phosphatase (ALP) staining, qPCR and western blotting. This study demonstrated that metformin significantly attenuated osteopenia, decreased serum glucose and glycated serum protein (GSP) levels, improved bone microarchitecture, and biomechanical properties in GK rats with T2DM. Metformin significantly increased biomarkers of bone formation, and significantly decreased muscle ubiquitin C (Ubc) expression. Network pharmacology analysis found that signal transducer and activator of transcription1 (STAT1) would be a potential target of metformin for regulating bone metabolism. Metformin increased C3H10 cell viability in vitro, alleviated ALP inhibition caused by hyperglycemia, increased the osteogenic gene expression of runt-related transcription factor 2 (RUNX2), collagen type I alpha 1 (Col1a1), osteocalcin (OCN), and ALP, while suppressing RAGE and STAT1 expression. Metformin also increased the protein expression of Osterix and decreased that of RAGE, p-JAK2, and p-STAT1. Our results demonstrate that metformin attenuated osteopenia and improved bone microarchitecture in GK rats with T2DM and significantly promoted stem cell osteogenic differentiation under high glucose condition. The effects of metformin on bone metabolism are closely associated with the suppression of RAGE-JAK2-STAT1 signaling axis. Our research provides experiment evidence and potential mechanistic rationale for the use of metformin as an effective candidate for diabetes-induced osteopenia treatment." @default.
- W4379259501 created "2023-06-04" @default.
- W4379259501 creator A5008807672 @default.
- W4379259501 creator A5009042071 @default.
- W4379259501 creator A5015545291 @default.
- W4379259501 creator A5023409618 @default.
- W4379259501 creator A5023430013 @default.
- W4379259501 creator A5026494857 @default.
- W4379259501 creator A5029982064 @default.
- W4379259501 creator A5032845247 @default.
- W4379259501 creator A5040776761 @default.
- W4379259501 creator A5043643054 @default.
- W4379259501 creator A5046876854 @default.
- W4379259501 creator A5053204257 @default.
- W4379259501 creator A5078230648 @default.
- W4379259501 creator A5079153908 @default.
- W4379259501 creator A5081771675 @default.
- W4379259501 date "2023-05-01" @default.
- W4379259501 modified "2023-09-30" @default.
- W4379259501 title "Metformin attenuates diabetes-induced osteopenia in rats is associated with down-regulation of the RAGE-JAK2-STAT1 signal axis" @default.
- W4379259501 cites W1589880213 @default.
- W4379259501 cites W1623101342 @default.
- W4379259501 cites W1820575250 @default.
- W4379259501 cites W1827885532 @default.
- W4379259501 cites W1837763023 @default.
- W4379259501 cites W1971079719 @default.
- W4379259501 cites W1977548231 @default.
- W4379259501 cites W1979388970 @default.
- W4379259501 cites W1986014108 @default.
- W4379259501 cites W1991429513 @default.
- W4379259501 cites W2013184426 @default.
- W4379259501 cites W2021188790 @default.
- W4379259501 cites W2032083061 @default.
- W4379259501 cites W2032184678 @default.
- W4379259501 cites W2045586178 @default.
- W4379259501 cites W2049467938 @default.
- W4379259501 cites W2056784246 @default.
- W4379259501 cites W2061450074 @default.
- W4379259501 cites W2068899618 @default.
- W4379259501 cites W2079063904 @default.
- W4379259501 cites W2080207036 @default.
- W4379259501 cites W2085133650 @default.
- W4379259501 cites W2096425957 @default.
- W4379259501 cites W2101579318 @default.
- W4379259501 cites W2102138162 @default.
- W4379259501 cites W2105731956 @default.
- W4379259501 cites W2117381673 @default.
- W4379259501 cites W2122566946 @default.
- W4379259501 cites W2125637498 @default.
- W4379259501 cites W2137106285 @default.
- W4379259501 cites W2140855999 @default.
- W4379259501 cites W2141260918 @default.
- W4379259501 cites W2147803180 @default.
- W4379259501 cites W2154459047 @default.
- W4379259501 cites W2160088494 @default.
- W4379259501 cites W2174310885 @default.
- W4379259501 cites W2508121467 @default.
- W4379259501 cites W2525729089 @default.
- W4379259501 cites W2527338241 @default.
- W4379259501 cites W2529327478 @default.
- W4379259501 cites W2801777656 @default.
- W4379259501 cites W2805127489 @default.
- W4379259501 cites W2902746975 @default.
- W4379259501 cites W2904861590 @default.
- W4379259501 cites W2911958614 @default.
- W4379259501 cites W2954472346 @default.
- W4379259501 cites W2954887528 @default.
- W4379259501 cites W3003926995 @default.
- W4379259501 cites W3014468869 @default.
- W4379259501 cites W3032313917 @default.
- W4379259501 cites W3048813625 @default.
- W4379259501 cites W3110510915 @default.
- W4379259501 cites W3128811528 @default.
- W4379259501 cites W3160963194 @default.
- W4379259501 cites W3183479640 @default.
- W4379259501 cites W3197209551 @default.
- W4379259501 cites W3201257544 @default.
- W4379259501 cites W4200533463 @default.
- W4379259501 cites W4206452518 @default.
- W4379259501 cites W4213331596 @default.
- W4379259501 cites W4281714801 @default.
- W4379259501 cites W4283069371 @default.
- W4379259501 cites W4296579967 @default.
- W4379259501 cites W4307199210 @default.
- W4379259501 doi "https://doi.org/10.1016/j.jot.2023.05.002" @default.
- W4379259501 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37304218" @default.
- W4379259501 hasPublicationYear "2023" @default.
- W4379259501 type Work @default.
- W4379259501 citedByCount "1" @default.
- W4379259501 countsByYear W43792595012023 @default.
- W4379259501 crossrefType "journal-article" @default.
- W4379259501 hasAuthorship W4379259501A5008807672 @default.
- W4379259501 hasAuthorship W4379259501A5009042071 @default.
- W4379259501 hasAuthorship W4379259501A5015545291 @default.
- W4379259501 hasAuthorship W4379259501A5023409618 @default.
- W4379259501 hasAuthorship W4379259501A5023430013 @default.
- W4379259501 hasAuthorship W4379259501A5026494857 @default.
- W4379259501 hasAuthorship W4379259501A5029982064 @default.