國家衛生研究院 NHRI:Item 3990099045/11885

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Title:	Cooperative impact of thiazolidinedione and fatty acid synthase on human osteogenesis
Authors:	Chen, CY;Tseng, KY;Wong, ZH;Chen, YP;Chen, TY;Chen, HY;Chen, ZY;Lin, FH;Wu, HM;Lin, S
Contributors:	Institute of Biomedical Engineering and Nanomedicine;National Institute of Infectious Diseases and Vaccinology
Abstract:	Previous, we found that the small molecules capable of inhibiting the expression and the pro-adipogenic activity of ZNF521 might improve the osteogenic performance of aging human bone marrow MSCs (bmMSCs), and that fatty acid synthase (FASN) was a critical effector of ZNF521's pro-adipogenic activity. Here, by characterizing the netoglitazone (MCC-555), one of the thiazolidinediones known as adipogenic enhancers, as an inhibitor of ZNF521 expression, we found that MCC-555 indeed also harbored pro-osteoblastic effect. Investigation revealed that MCC-555 might function as a GSK3beta inhibitor to promote osteoblastogenesis and bone formation. Importantly, combination of MCC-555 with FASN knockdown, but not with GW9662 (a PPARgamma2 antagonist), blocked the pro-adipogenic but retained the pro-osteoblastic effect of MCC-555. Using a 3-dimentional culture system, we showed that MCC-555 facilitated the FASN-knockdown of aging human bmMSCs to form cell clusters in scaffolds, and to promote osteoblastic differentiation and biomineralization in cell clusters. These data indicated that MCC-555 promoted bmMSCs to produce bone-like tissues. Our data narrate a thiazolidinedione-based novel strategy to improve the osteogenic performance of aging bmMSCs to support the application of autologous aging bmMSCs in cell therapy and in producing bone-like tissues for repairing bone injury in the elderly.
Date:	2019-04-20
Relation:	Aging. 2019 Apr 20;11(8):2327-2342.
Link to:	http://dx.doi.org/10.18632/aging.101916
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1945-4589&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000466768900013
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85065597141
Appears in Collections:	[Feng-Huei Lin] Periodical Articles [Others] Periodical Articles

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