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Published on: May 4, 2018
PKD1 alleviates oxidative stress-inhibited osteogenesis of rat bone marrow-derived mesenchymal stem cells through TAZ
Tongtong Chen1, Hanqi Wang1, Chaoyin Jiang2,3
1Department of Radiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Abstract:
Oxidative stress is known to inhibit osteogenesis and PKD1 is implicated in bone remodeling and skeletogenesis. In the present study, we explored the role of PKD1 in osteogenesis under oxidative stress. H2 O2 was used to induce oxidative stress in rat bone marrow (BM)-mesenchymal stem cells (MSCs) during osteoblast differentiation. Alkaline phosphatase (ALP) activity, calcium deposits, and the RUNX2 marker were assayed to determine osteogenic differentiation. The correlation of PKD1, Sirt1, c-MYC, and TAZ was further confirmed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. We found that H2 O2 induced the downregulation of PKD1 expression and the upregulation of c-MYC, and Sirt1 was accompanied by decreasing cell viability in BM-MSCs. During osteogenic differentiation, the expression of PKD1 was upregulated significantly whereas Sirt1 tended to be upregulated mildly under normal conditions. Both PKD1 and Sirt1 were upregulated upon oxidative stress. The positive correlation of PKD1 expression with osteogenic differentiation under normal conditions might be hindered by oxidative stress and PKD1 could interact with TAZ under oxidative stress to regulate osteogenic differentiation. Our results suggest that PKD1 may alleviate oxidative stress-inhibited osteogenesis of rat BM-MSCs through TAZ activation.
Insights
Polycystic kidney disease 1 (PKD1) may protect against oxidative stress-induced bone loss. This study shows PKD1 activation alleviates oxidative stress, promoting osteogenesis in rat bone marrow stem cells.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Oxidative stress impairs osteogenesis, crucial for bone remodeling.
- Polycystic kidney disease 1 (PKD1) plays a role in bone development and repair.
Purpose of the Study:
- To investigate the function of PKD1 in osteogenesis under oxidative stress conditions.
- To elucidate the molecular mechanisms by which PKD1 influences osteoblast differentiation.
Main Methods:
- Rat bone marrow mesenchymal stem cells (BM-MSCs) were subjected to hydrogen peroxide (H2O2) to induce oxidative stress.
- Osteogenic differentiation was assessed by measuring alkaline phosphatase (ALP) activity, calcium deposition, and RUNX2 expression.
- Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to confirm molecular interactions.
Main Results:
- H2O2 downregulated PKD1 and decreased cell viability, while upregulating c-MYC and Sirt1.
- Under normal conditions, PKD1 was significantly upregulated during osteogenesis.
- Both PKD1 and Sirt1 were upregulated under oxidative stress, with PKD1 potentially interacting with TAZ to regulate differentiation.
Conclusions:
- PKD1 expression is crucial for osteogenic differentiation.
- PKD1 may counteract the inhibitory effects of oxidative stress on osteogenesis in rat BM-MSCs.
- PKD1's protective role is potentially mediated through TAZ activation under oxidative stress.
