Počet záznamů: 1
Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones
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SYSNO ASEP 0562691 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones Tvůrce(i) Beňová, Andrea (FGU-C) ORCID
Ferenčáková, Michaela (FGU-C) ORCID, RID
Bardová, Kristina (FGU-C) RID, ORCID, SAI
Funda, Jiří (FGU-C) ORCID
Procházka, Jan (UMG-J) ORCID
Špoutil, František (UMG-J)
Čajka, Tomáš (FGU-C) RID, ORCID, SAI
Džubanová, Martina (FGU-C) ORCID
Balcaen, T. (BE)
Kerckhofs, G. (BE)
Willekens, W. (BE)
van Lenthe, G. H. (BE)
Alquicer, Glenda (FGU-C) ORCID
Pecinová, Alena (FGU-C) RID, ORCID, SAI
Mráček, Tomáš (FGU-C) RID, ORCID
Horáková, Olga (FGU-C) RID, ORCID
Rossmeisl, Martin (FGU-C) RID, ORCID
Kopecký, Jan (FGU-C) RID, ORCID
Tencerová, Michaela (FGU-C) RID, ORCIDČíslo článku 101598 Zdroj.dok. Molecular Metabolism. - : Elsevier - ISSN 2212-8778
Roč. 65, Nov (2022)Poč.str. 20 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova obesity-induced bone fragility ; bone microstructure ; bone marrow mesenchymal stem cells ; bone marrow adiposity ; thiazolidinedione analog MSDC-0602K ; pioglitazone Obor OECD Physiology (including cytology) CEP GA20-03586S GA ČR - Grantová agentura ČR GA19-02411S GA ČR - Grantová agentura ČR LX22NPO5104 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 ; UMG-J - RVO:68378050 UT WOS 000872604500004 EID SCOPUS 85138149646 DOI 10.1016/j.molmet.2022.101598 Anotace Objective: The use of thiazolidinediones (TZDs) as insulin sensitizers has been shown to have side effects including increased accumulation of bone marrow adipocytes (BMAds) associated with a higher fracture risk and bone loss. A novel TZD analog MSDC-0602K with low affinity to PPARγ has been developed to reduce adverse effects of TZD therapy. However, the effect of MSDC-0602K on bone phenotype and bone marrow mesenchymal stem cells (BM-MSCs) in relation to obesity has not been intensively studied yet.
Methods:Here, we investigated whether 8-week treatment with MSDC-0602K has a less detrimental effect on bone loss and BM-MSC properties in obese mice in comparison to first generation of TZDs, pioglitazone. Bone parameters (bone microstructure, bone marrow adiposity, bone strength) were examined by μCT and 3-point bending test. Primary BM-MSCs were isolated and measured for osteoblast and adipocyte differentiation. Cellular senescence, bioenergetic profiling, nutrient consumption and insulin signaling were also determined.Results:The findings demonstrate that MSDC-0602K improved bone parameters along with increased proportion of smaller BMAds in tibia of obese mice when compared to pioglitazone. Further, primary BM-MSCs isolated from treated mice and human BM-MSCs revealed decreased adipocyte and higher osteoblast differentiation accompanied with less inflammatory and senescent phenotype induced by MSDC-0602K vs. pioglitazone. These changes were further reflected by increased glycolytic activity differently affecting glutamine and glucose cellular metabolism in MSDC-0602K-treated cells compared to pioglitazone, associated with higher osteogenesis.Conclusion:Our study provides novel insights into the action of MSDC-0602K in obese mice, characterized by the absence of detrimental effects on bone quality and BM-MSC metabolism when compared to classical TZDs and thus suggesting a potential therapeutical use of MSDC-0602K in both metabolic and bone diseases.Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2023 Elektronická adresa https://doi.org/10.1016/j.molmet.2022.101598
Počet záznamů: 1