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Calcium phytate reverses high glucose-inhibited osteogenesis of BMSCs via the MAPK/JNK pathway
Jiaxin Lv1,2, Qiaona Wang2,3, Dongyu Liu1,2
1Department of Dental Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Objectives:
Diabetes mellitus (DM) induces oxidative tissue impairment and suppresses bone formation. Some studies have shown that phytic acid has antioxidant and anti-diabetic properties. This study aimed to investigate the potential of calcium phytate (Ca-phytate) to reverse inhibited osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) in a high glucose (HG) environment and to determine the underlying mechanism.
Materials And Methods:
hBMSCs were exposed to HG and palmitic acid to simulate DM in vitro. Osteogenic differentiation was measured using alkaline phosphatase staining and activity assay, alizarin red S staining, qRT-PCR, Western blot and immunofluorescence staining. A critical-size cranial defect model of type 2 diabetes mellitus (T2DM) rats was established to evaluate bone regeneration. A specific pathway inhibitor was used to explore whether the MAPK/JNK pathway was involved.
Results:
Treatment with 34 μM Ca-phytate had the highest effect on osteogenic differentiation in HG. Ca-phytate improved cranial bone defect healing in T2DM rats. The long-term HG environment inhibited the activation of the MAPK/JNK signalling pathway, which was restored by Ca-phytate. Blocking the JNK pathway reduced the Ca-phytate-mediated osteogenic differentiation of hBMSCs.
Conclusion:
Ca-phytate induced bone regeneration in vivo and reversed HG-inhibited osteogenesis of hBMSCs in vitro via the MAPK/JNK signalling pathway.
Insights
Calcium phytate (Ca-phytate) promotes bone regeneration in diabetic rats and reverses high glucose-inhibited osteogenesis in human bone marrow mesenchymal stem cells (hBMSCs) by activating the MAPK/JNK pathway.
Area of Science:
- Biomaterials Science
- Stem Cell Biology
- Endocrinology
Background:
- Diabetes mellitus (DM) impairs bone formation and causes oxidative stress.
- Phytic acid exhibits antioxidant and anti-diabetic properties.
- Osteogenesis in human bone marrow mesenchymal stem cells (hBMSCs) is inhibited by high glucose (HG).
Purpose of the Study:
- To investigate calcium phytate's (Ca-phytate) potential to reverse HG-induced inhibition of osteogenesis in hBMSCs.
- To elucidate the underlying molecular mechanisms, focusing on the MAPK/JNK pathway.
- To evaluate Ca-phytate's efficacy in promoting bone regeneration in a type 2 diabetes mellitus (T2DM) rat model.
Main Methods:
- Simulated DM in vitro using HG and palmitic acid on hBMSCs.
- Assessed osteogenic differentiation via alkaline phosphatase, alizarin red S staining, qRT-PCR, Western blot, and immunofluorescence.
- Utilized a T2DM rat cranial defect model and MAPK/JNK pathway inhibitors.
Main Results:
- Ca-phytate at 34 μM significantly enhanced osteogenic differentiation in HG conditions.
- Ca-phytate treatment accelerated cranial bone defect healing in T2DM rats.
- Ca-phytate restored MAPK/JNK pathway activation inhibited by HG, and JNK pathway blockade diminished Ca-phytate's osteogenic effects.
Conclusions:
- Ca-phytate effectively induces bone regeneration in vivo and reverses HG-impaired osteogenesis in hBMSCs.
- The pro-osteogenic effects of Ca-phytate are mediated through the MAPK/JNK signaling pathway.
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