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High glucose inhibits osteogenic differentiation through the BMP signaling pathway in bone mesenchymal stem cells in mice.

Wang J, Wang B, Li Y, Wang D, Lingling E, Bai Y, Liu H - EXCLI J (2013)

Bottom Line: The intracellular BMP-2 level in BMSCs cultured in a high-glucose microenvironment was significantly decreased and suppressed activation of the BMP signaling pathway.Consequently, expression of the osteogenic markers Runx2, alkaline phosphatase, and osteocalcin were decreased.Thus, it is possible that agents modifying this pathway could be used by BMSCs to promote bone regeneration in high-glucose microenvironments.

View Article: PubMed Central - PubMed

Affiliation: Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.

ABSTRACT
Patients with diabetes tend to have an increased risk of osteoporosis that may be related to hyperglycemia. In vitro evidence has shown that high glucose can affect the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs). Tissue regeneration depends mainly on MSCs. However, the exact mechanisms involved in high glucose-induced bone loss remain unknown. In this study, we investigated the effects of high glucose on the proliferation and osteogenic differentiation of mice bone MSCs (BMSCs) and determined the specific mechanism of bone morphogenetic protein 2 (BMP-2) in the osteogenic differentiation of mice BMSCs in a high-glucose microenvironment. High glucose (< 25 mM) promoted cell growth but suppressed mineralization. The intracellular BMP-2 level in BMSCs cultured in a high-glucose microenvironment was significantly decreased and suppressed activation of the BMP signaling pathway. Consequently, expression of the osteogenic markers Runx2, alkaline phosphatase, and osteocalcin were decreased. Meanwhile, supplementation with ectogenic BMP-2 reversed the cell osteogenic differentiation and osteogenic marker down-regulation under high glucose. Our data indicate that BMP-2 plays an important role in regulating the osteogenic differentiation of BMSCs in a high-glucose microenvironment. Thus, it is possible that agents modifying this pathway could be used by BMSCs to promote bone regeneration in high-glucose microenvironments.

No MeSH data available.


Related in: MedlinePlus

High glucose had an inhibitory effect on BMSC osteogenic differentiation.A: BMSCs were cultured in four osteogenic media (glucose concentrations: 5.5 mM, 16.5 mM, 25 mM, and 35 mM, respectively) for 21 days; mineralized nodules were detected following Alizarin red S staining. Scale bars represent 100 µm.B: Graph illustrating the quantitative evaluation of Alizarin red S staining of the four groups. *P < 0.05 vs. the normal/Diff group
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Figure 2: High glucose had an inhibitory effect on BMSC osteogenic differentiation.A: BMSCs were cultured in four osteogenic media (glucose concentrations: 5.5 mM, 16.5 mM, 25 mM, and 35 mM, respectively) for 21 days; mineralized nodules were detected following Alizarin red S staining. Scale bars represent 100 µm.B: Graph illustrating the quantitative evaluation of Alizarin red S staining of the four groups. *P < 0.05 vs. the normal/Diff group

Mentions: The Alizarin red S staining showed that the mineralization of BMSCs was inhibited by high glucose (16.5 - 35 mM) on day 21 (Figure 2A(Fig. 2)). Inverted microscopy revealed that the number and size of mineral nodules decreased as the glucose concentration increased. It was extremely difficult to detect typical mineral nodules in the BMSCs grown in medium containing 35 mM glucose. The optical density values from the Alizarin red S staining quantification were 0.440, 0.303, 0.262, and 0.113 in 5.5 mM, 16.5 mM, 25 mM, and 35 mM glucose, respectively, indicating a negative relationship between osteogenic ability and high glucose concentration (P < 0.01; Figure 2B(Fig. 2)). Based on the effects of high glucose on the proliferation and osteogenic differentiation of the BMSCs, we selected 5.5 mM glucose as the normal group (control) and 25 mM glucose as the high-glucose group for further experiments.


High glucose inhibits osteogenic differentiation through the BMP signaling pathway in bone mesenchymal stem cells in mice.

Wang J, Wang B, Li Y, Wang D, Lingling E, Bai Y, Liu H - EXCLI J (2013)

High glucose had an inhibitory effect on BMSC osteogenic differentiation.A: BMSCs were cultured in four osteogenic media (glucose concentrations: 5.5 mM, 16.5 mM, 25 mM, and 35 mM, respectively) for 21 days; mineralized nodules were detected following Alizarin red S staining. Scale bars represent 100 µm.B: Graph illustrating the quantitative evaluation of Alizarin red S staining of the four groups. *P < 0.05 vs. the normal/Diff group
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834668&req=5

Figure 2: High glucose had an inhibitory effect on BMSC osteogenic differentiation.A: BMSCs were cultured in four osteogenic media (glucose concentrations: 5.5 mM, 16.5 mM, 25 mM, and 35 mM, respectively) for 21 days; mineralized nodules were detected following Alizarin red S staining. Scale bars represent 100 µm.B: Graph illustrating the quantitative evaluation of Alizarin red S staining of the four groups. *P < 0.05 vs. the normal/Diff group
Mentions: The Alizarin red S staining showed that the mineralization of BMSCs was inhibited by high glucose (16.5 - 35 mM) on day 21 (Figure 2A(Fig. 2)). Inverted microscopy revealed that the number and size of mineral nodules decreased as the glucose concentration increased. It was extremely difficult to detect typical mineral nodules in the BMSCs grown in medium containing 35 mM glucose. The optical density values from the Alizarin red S staining quantification were 0.440, 0.303, 0.262, and 0.113 in 5.5 mM, 16.5 mM, 25 mM, and 35 mM glucose, respectively, indicating a negative relationship between osteogenic ability and high glucose concentration (P < 0.01; Figure 2B(Fig. 2)). Based on the effects of high glucose on the proliferation and osteogenic differentiation of the BMSCs, we selected 5.5 mM glucose as the normal group (control) and 25 mM glucose as the high-glucose group for further experiments.

Bottom Line: The intracellular BMP-2 level in BMSCs cultured in a high-glucose microenvironment was significantly decreased and suppressed activation of the BMP signaling pathway.Consequently, expression of the osteogenic markers Runx2, alkaline phosphatase, and osteocalcin were decreased.Thus, it is possible that agents modifying this pathway could be used by BMSCs to promote bone regeneration in high-glucose microenvironments.

View Article: PubMed Central - PubMed

Affiliation: Department of Stomatology, Chinese PLA General Hospital and Postgraduate Military Medical School, Beijing 100853, China.

ABSTRACT
Patients with diabetes tend to have an increased risk of osteoporosis that may be related to hyperglycemia. In vitro evidence has shown that high glucose can affect the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs). Tissue regeneration depends mainly on MSCs. However, the exact mechanisms involved in high glucose-induced bone loss remain unknown. In this study, we investigated the effects of high glucose on the proliferation and osteogenic differentiation of mice bone MSCs (BMSCs) and determined the specific mechanism of bone morphogenetic protein 2 (BMP-2) in the osteogenic differentiation of mice BMSCs in a high-glucose microenvironment. High glucose (< 25 mM) promoted cell growth but suppressed mineralization. The intracellular BMP-2 level in BMSCs cultured in a high-glucose microenvironment was significantly decreased and suppressed activation of the BMP signaling pathway. Consequently, expression of the osteogenic markers Runx2, alkaline phosphatase, and osteocalcin were decreased. Meanwhile, supplementation with ectogenic BMP-2 reversed the cell osteogenic differentiation and osteogenic marker down-regulation under high glucose. Our data indicate that BMP-2 plays an important role in regulating the osteogenic differentiation of BMSCs in a high-glucose microenvironment. Thus, it is possible that agents modifying this pathway could be used by BMSCs to promote bone regeneration in high-glucose microenvironments.

No MeSH data available.


Related in: MedlinePlus