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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

BMP signaling pathway in BMSCs was inhibited in high-glucose microenvironment.A: BMP-2 levels were tested after BMSCs were grown in normal or high-glucose osteogenic medium for seven days. β-actin was used as an internal control.B: Scanned images of ALP staining of BMSC after 7-d culture in osteogenic medium containing normal (5.5 mM) or high glucose (25 mM). Graph depicts the quantitative evaluation of ALP activity. The results represent the mean ± SD. *P < 0.05 vs. the normal/Diff group, n = 3C: Real-time PCR analysis of RUNX2, ALP, and OCN expression in normal and high-glucose conditions grown in basal (Undiff) or osteogenic medium (Diff) for 7 d. The expression levels were normalized to that of β-actin. The results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal/Diff group
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Figure 3: BMP signaling pathway in BMSCs was inhibited in high-glucose microenvironment.A: BMP-2 levels were tested after BMSCs were grown in normal or high-glucose osteogenic medium for seven days. β-actin was used as an internal control.B: Scanned images of ALP staining of BMSC after 7-d culture in osteogenic medium containing normal (5.5 mM) or high glucose (25 mM). Graph depicts the quantitative evaluation of ALP activity. The results represent the mean ± SD. *P < 0.05 vs. the normal/Diff group, n = 3C: Real-time PCR analysis of RUNX2, ALP, and OCN expression in normal and high-glucose conditions grown in basal (Undiff) or osteogenic medium (Diff) for 7 d. The expression levels were normalized to that of β-actin. The results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal/Diff group

Mentions: Recent studies have demonstrated that the BMP pathway appears to play an important role in MSC osteogenic differentiation (Lin and Hankenson, 2011[24]) and BMP-2, which is a key protein of the BMP signaling pathway, was altered in high-glucose conditions (Chen et al., 2006[4]). Thus, we postulated that the high-glucose microenvironment would inhibit the BMP signaling pathway during the osteogenic differentiation process. In the present study, the expression of BMP-2 was investigated following culture in osteogenic medium (containing 5.5 or 25 mM glucose) for seven days. Our data revealed that BMP-2 levels were increased in BMSCs cultured in osteogenic medium (containing 5.5 mM or 25 mM glucose) relative to the control. Additionally, the BMP-2 concentration was lower in the BMSCs cultured under high-glucose osteogenic conditions compared to those ltured in normal glucose osteogenic conditions (Figure 3A(Fig. 3)).


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)

BMP signaling pathway in BMSCs was inhibited in high-glucose microenvironment.A: BMP-2 levels were tested after BMSCs were grown in normal or high-glucose osteogenic medium for seven days. β-actin was used as an internal control.B: Scanned images of ALP staining of BMSC after 7-d culture in osteogenic medium containing normal (5.5 mM) or high glucose (25 mM). Graph depicts the quantitative evaluation of ALP activity. The results represent the mean ± SD. *P < 0.05 vs. the normal/Diff group, n = 3C: Real-time PCR analysis of RUNX2, ALP, and OCN expression in normal and high-glucose conditions grown in basal (Undiff) or osteogenic medium (Diff) for 7 d. The expression levels were normalized to that of β-actin. The results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal/Diff group
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: BMP signaling pathway in BMSCs was inhibited in high-glucose microenvironment.A: BMP-2 levels were tested after BMSCs were grown in normal or high-glucose osteogenic medium for seven days. β-actin was used as an internal control.B: Scanned images of ALP staining of BMSC after 7-d culture in osteogenic medium containing normal (5.5 mM) or high glucose (25 mM). Graph depicts the quantitative evaluation of ALP activity. The results represent the mean ± SD. *P < 0.05 vs. the normal/Diff group, n = 3C: Real-time PCR analysis of RUNX2, ALP, and OCN expression in normal and high-glucose conditions grown in basal (Undiff) or osteogenic medium (Diff) for 7 d. The expression levels were normalized to that of β-actin. The results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal/Diff group
Mentions: Recent studies have demonstrated that the BMP pathway appears to play an important role in MSC osteogenic differentiation (Lin and Hankenson, 2011[24]) and BMP-2, which is a key protein of the BMP signaling pathway, was altered in high-glucose conditions (Chen et al., 2006[4]). Thus, we postulated that the high-glucose microenvironment would inhibit the BMP signaling pathway during the osteogenic differentiation process. In the present study, the expression of BMP-2 was investigated following culture in osteogenic medium (containing 5.5 or 25 mM glucose) for seven days. Our data revealed that BMP-2 levels were increased in BMSCs cultured in osteogenic medium (containing 5.5 mM or 25 mM glucose) relative to the control. Additionally, the BMP-2 concentration was lower in the BMSCs cultured under high-glucose osteogenic conditions compared to those ltured in normal glucose osteogenic conditions (Figure 3A(Fig. 3)).

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