Naringin protects human adipose-derived mesenchymal stem cells against hydrogen peroxide-induced inhibition of osteogenic differentiation.
Extensive evidence indicates that oxidative stress plays a pivotal role in the development of osteoporosis. We show that naringin, a natural antioxidant and anti-inflammatory compound, effectively protects human adipose-derived mesenchymal stem cells (hADMSCs) against hydrogen peroxide (H2O2)-induced inhibition of osteogenic differentiation. Naringin increased viability of hAMDSCs and attenuated H2O2-induced cytotoxicity. Naringin also reversed H2O2-induced oxidative stress. Oxidative stress induced by H2O2 inhibits osteogenic differentiation by decreasing alkaline phosphatase (ALP) activity, calcium content and mRNA expression levels of osteogenesis marker genes RUNX2 and OSX in hADMSCs. However, addition of naringin leads to a significant recovery, suggesting the protective effects of naringin against H2O2-induced inhibition of osteogenic differentiation. Furthermore, the H2O2-induced decrease of protein expressions of β-catenin and clyclin D1, two important transcriptional regulators of Wnt-signaling, was successfully rescued by naringin treatment. Also, in the presence of Wnt inhibitor DKK-1, naringin is no longer effective in stimulating ALP activity, increasing calcium content and mRNA expression levels of RUNX2 and OSX in H2O2-exposed hADMSCs. These data clearly demonstrates that naringin protects hADMSCs against oxidative stress-induced inhibition of osteogenic differentiation, which may involve Wnt signaling pathway. Our work suggests that naringin may be a useful addition to the treatment armamentarium for osteoporosis and activation of Wnt signaling may represent attractive therapeutic strategy for the treatment of degenerative disease of bone tissue.
Department of Joint Surgery, Affiliated Hospital of Jining Medical University, 79 Guhuai Road, Jining 272000, Shandong, China.
Lei
L
Wang
Department of Joint Surgery, Affiliated Hospital of Jining Medical University, 79 Guhuai Road, Jining 272000, Shandong, China.
Yu-Ge
YG
Zhang
Department of Electroencephalogram, Affiliated Hospital of Jining Medical University, 79 Guhuai Road, Jining 272000, Shandong, China.
Xiu-Mei
XM
Wang
Department of Joint Surgery, Affiliated Hospital of Jining Medical University, 79 Guhuai Road, Jining 272000, Shandong, China.
Long-Fei
LF
Ma
Department of Joint Surgery, Affiliated Hospital of Jining Medical University, 79 Guhuai Road, Jining 272000, Shandong, China. Electronic address: zymjn@sina.com.
Yuan-Min
YM
Zhang
D000273:Adipose Tissue / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
D044950:Flavanones; D006861:Hydrogen Peroxide; C005274:naringin
Human adipose-derived mesenchymal stem cells; Naringin; Osteogenic differentiation; Oxidative stress; Wnt signaling