Linxiao Xu1, Xinyunxi He1, Yuanyi Zhou1, Kailing Yu1, Mingyue Yuan1, Qiaoyan Zhang1, Luping Qin1, Quanlong Zhang1.
Abstract
AIMS: 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
AIMS: 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities:
Keywords:
Fisetin; MC3T3-E1 cell; PI3K-AKT signaling pathway.; connectivity map assay; osteoporosis
Mesh：
Substances：
Year: 2021
PMID： 33645479 DOI： 10.2174/1389201022666210301141238
Source DB: PubMed Journal: Curr Pharm Biotechnol ISSN： 1389-2010 Impact factor: 2.837