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Updated: Oct 23, 2025
Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and Osteoclast Progenitors from Mice
Published on: January 6, 2018
Advanced glycosylation end products inhibit the proliferation of bone-marrow stromal cells through activating MAPK
Zheng Li1, Xiao Wang2, Tian-Pei Hong3
1Department of Stomatology, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing, 100191, China.
Background:
The purpose of present study was to explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) on rat bone-marrow stromal cells (BMSCs).
Methods:
Prepare and identify AGEs. BMSCs were isolated from 16 SD rats and cultured with different concentration of AGEs. Cell viability was detected by cell counting kit-8 (CCK-8). BMSCs were cultured with AGEs (0.25 mg/ml) for 30 min, 12 h, 24 h, 72 h and 120 h. In addition, BMSCs were cultured with AGEs, AGEs + JNK inhibitor and AGEs + P38 inhibitor for 24 h and 48 h, respectively. Western blotting and RT-PCR were used to determine the protein and mRNA expression levels, respectively.
Results:
Cell viability of BMSCs was significantly correlated with concentration and effect time of AGEs (P < 0.05), and the most appropriate concentration was 0.25 mg/ml. AGEs stimulation significantly increased the protein expression levels of NF-κB p65, JNK, p38 (P < 0.05), decreased IκB (P < 0.05), but had no effect on the protein expression of Akt in BMSCs (P > 0.05). At the mRNA level, JNK and p38 inhibitors significantly reduced the levels of NF-κB p65, p38 and JNK, increased IκB (P > 0.05), but had no effect on Akt in BMSCs (P > 0.05). At the protein level, JNK and p38 inhibitors notably decreased the expression of NF-κB p65, p38, p-JNK, P-IκB and JNK (P < 0.001), and increased IκB (P < 0.05).
Conclusion:
Advanced glycosylation end products can inhibit the proliferation of bone-marrow stromal cells through activating MAPK pathway.
Insights
Advanced glycosylation end products (AGEs) inhibit bone-marrow stromal cell proliferation by activating the MAPK pathway. This study elucidates the signaling mechanisms involved in AGEs-induced cellular responses.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Advanced glycosylation end products (AGEs) are implicated in cellular dysfunction.
- Signaling pathways like NF-κB, PI3K/Akt, and MAPK are crucial in cellular responses.
- Understanding AGEs' impact on bone-marrow stromal cells (BMSCs) is vital for regenerative medicine.
Purpose of the Study:
- To investigate the mechanistic role of NF-κB, PI3K/Akt, and MAPK signaling pathways.
- To determine the effects of AGEs intervention on rat BMSCs.
- To elucidate the signaling cascade triggered by AGEs in BMSCs.
Main Methods:
- BMSCs were isolated from Sprague-Dawley rats and cultured with varying AGEs concentrations.
- Cell viability was assessed using CCK-8 assay.
- Protein and mRNA expression levels were analyzed via Western blotting and RT-PCR, respectively, with and without pathway inhibitors.
Main Results:
- AGEs significantly impacted BMSC viability in a dose- and time-dependent manner (P<0.05).
- AGEs upregulated NF-κB p65, JNK, and p38, while downregulating IκB.
- MAPK pathway inhibitors (JNK and p38) reduced NF-κB p65 expression and modulated IκB levels, indicating pathway crosstalk.
Conclusions:
- Advanced glycosylation end products inhibit BMSC proliferation.
- The mitogen-activated protein kinase (MAPK) pathway is a key mediator of AGEs' inhibitory effects on BMSCs.
- These findings highlight the role of MAPK signaling in AGEs-induced cellular damage.
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