Fibroblast growth factor-2 ameliorates tumor necrosis factor-alpha-induced osteogenic damage of human bone
Yishan Hao1, Minting Wu1, Jinming Wang1
1Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Abstract:
Tumor necrosis factor-alpha (TNF-α) has been shown to have an inhibitory effect on the osteogenic differentiation of mesenchymal stem cells. The metabolic switch from glycolysis to oxidative phosphorylation (OXPHOS) is vital for energy supply during osteogenic differentiation. However, the metabolic switch is inhibited under inflammatory stimulation. FGF2 has shown that it can improve osteogenic differentiation and promote autoimmune inflammation. In this study, we investigated whether FGF2 can ameliorate TNF-a-inhibited osteogenic damage by improving OXPHOS. Effects of TNF-α or FGF2 on the proliferation and osteogenic differentiation of hBMSCs were evaluated by MTT assay, qRT-PCR, and ALP activity tests. The function of FGF2 on the TNF-a-inhibited metabolic switch was determined by Mito Stress test. The results showed that TNF-α was able to inhibit the osteogenic differentiation and OXPHOS of hBMSCs. FGF2 has no obvious function in improving the osteogenic-related genes, but it can ameliorate the impaired osteogenesis and OCR value caused by TNF-α. These findings suggest that FGF2 can prevent the impaired osteogenic differentiation and metabolic switch of hBMSCs under inflammatory stimulation, which might enhance the regeneration capacity of hBMSCs.
Insights
Fibroblast Growth Factor 2 (FGF2) can protect human bone marrow stem cells (hBMSCs) from inflammation-induced damage. FGF2 ameliorates impaired osteogenesis and metabolic dysfunction caused by Tumor Necrosis Factor-alpha (TNF-α).
Area of Science:
- Biomedical Science
- Stem Cell Biology
- Metabolic Regulation
Background:
- Tumor Necrosis Factor-alpha (TNF-α) inhibits osteogenic differentiation of mesenchymal stem cells.
- Osteogenic differentiation relies on a metabolic switch to oxidative phosphorylation (OXPHOS), which is impaired by inflammation.
- Fibroblast Growth Factor 2 (FGF2) has potential roles in osteogenesis and inflammation.
Purpose of the Study:
- To investigate if FGF2 can mitigate TNF-α-induced inhibition of osteogenic differentiation in human bone marrow stem cells (hBMSCs).
- To determine if FGF2 can improve the metabolic switch to OXPHOS impaired by TNF-α.
Main Methods:
- MTT assay, qRT-PCR, and ALP activity tests assessed proliferation and osteogenic differentiation.
- Mito Stress test evaluated the effect of FGF2 on TNF-α-inhibited metabolic switch.
- Assessed oxygen consumption rate (OCR) to measure metabolic activity.
Main Results:
- TNF-α inhibited osteogenic differentiation and OXPHOS in hBMSCs.
- FGF2 did not significantly improve osteogenic gene expression independently.
- FGF2 ameliorated TNF-α-induced impairment of osteogenesis and reduced OCR.
Conclusions:
- FGF2 can prevent impaired osteogenic differentiation and metabolic dysfunction in hBMSCs under inflammatory conditions.
- FGF2 may enhance the regenerative capacity of hBMSCs by counteracting TNF-α effects.
- FGF2's role in metabolic regulation is crucial for stem cell function during inflammation.
