In:
Current Pharmaceutical Biotechnology, Bentham Science Publishers Ltd., Vol. 22, No. 15 ( 2021-12), p. 2038-2047
Abstract:
This research aimed at exploring potential new compounds to be used in the treatment
of osteoporosis by Connectivity Map (CMap) and determining the role of fisetin in osteoporosis according to its effects on the PI3K-AKT signaling pathway in MC3T3-E1 pre-osteoblastic cells. Methods: Microarray analysis was used to obtain the differentially expressed genes in published gene
expression data. Potent compounds for osteoporosis therapy were discovered by CMap analysis. DAVID and Gene Set Enrichment Analysis (GSEA) were used to discover signaling pathways that
connected to osteoporosis disease. Cell viability was evaluated by a CCK-8 assay. Quantitative realtime Polymerase Chain Reaction (qRT-PCR) and western blot analysis were used to test the mRNA
and protein expressions related to the PI3K-AKT signaling pathway in MC3T3-E1 cells, respectively. Results: CMap analysis identified fisetin as a promising compound for anti-osteoporosis treatment.
DAVID and GSEA analysis showed that the PI3K-AKT signaling pathway was inactivated in osteoporosis. Cell experiments revealed that fisetin caused an elevation of cell viability, up-regulated the
mRNA levels of the Runt-related transcription factor-2 (Runx2), Osterix (Osx), collagen type I 1 (Col1a1) and Osteoprotegerin (OPG) while down-regulated the nuclear factor-κB ligand (RANKL)
mRNA level. Discussion: The protein levels of Runx2, Col1a1 and Osteocalcin (OCN) were also increased by
fisetin. Furthermore, fisetin activated the phosphoinositide-3-kinase/protein kinase B (PI3K-AKT) signaling pathway, and blocking this pathway by the inhibitor LY-294002 could impair fisetin’s functions
on proliferation, differentiation and OPG/RANKL expression ratio in the MC3T3-E1 cells. Conclusion: Our results demonstrated that fisetin could promote MC3T3-E1 cell proliferation, differentiation
and increase OPG/RANKL expression ratio through activating the PI3K-AKT pathway, which has potential for the treatment of osteoporosis.
Type of Medium:
Online Resource
ISSN:
1389-2010
DOI:
10.2174/1389201022666210301141238
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2021
detail.hit.zdb_id:
2132197-8
SSG:
15,3
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