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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

Up-regulated expression levels of RUNX2 by BMP-2 promoted BMSC osteogenic differentiation in normal (5.5 mM) and high-glucose (25 mM) conditions.A: The level of endogenic BMP-2 in BMSCs grown in basal osteogenic medium containing normal (5.5 mM) or high glucose (25 mM), or in the absence or presence of BMP-2 (100 ng/mL) for 7 d were measured by Western blot.B: Real-time PCR analysis of RUNX2, ALP, and OCN expression in BMSCs after 7-d culture in basal medium (Undiff) and osteogenic medium (Diff), containing normal (5.5 mM) or high glucose (25 mM) in the absence or presence of 100 ng/mL BMP-2. β-Actin was used as a control for equal loading. Results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal /Diff groups
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Figure 4: Up-regulated expression levels of RUNX2 by BMP-2 promoted BMSC osteogenic differentiation in normal (5.5 mM) and high-glucose (25 mM) conditions.A: The level of endogenic BMP-2 in BMSCs grown in basal osteogenic medium containing normal (5.5 mM) or high glucose (25 mM), or in the absence or presence of BMP-2 (100 ng/mL) for 7 d were measured by Western blot.B: Real-time PCR analysis of RUNX2, ALP, and OCN expression in BMSCs after 7-d culture in basal medium (Undiff) and osteogenic medium (Diff), containing normal (5.5 mM) or high glucose (25 mM) in the absence or presence of 100 ng/mL BMP-2. β-Actin was used as a control for equal loading. Results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal /Diff groups

Mentions: BMP-2 is known to positively regulate osteogenic differentiation. To verify whether treatment of BMSCs with BMP-2 can promote osteogenic differentiation and rescue the osteogenic suppression of high glucose, we tested the intracellular BMP-2 levels and RUNX2, ALP, and OCN expression in the BMSCs after treatment with ectogenic BMP-2. The intracellular BMP-2 in both osteogenic groups (5.5 mM and 25 mM glucose) was significantly elevated (Figure 4A(Fig. 4)). The expression of RUNX2, ALP, and OCN was also increased by 1.72, 1.47, and 1.47-fold in BMP-2-treated BMSCs cultured in osteogenic medium containing 5.5 mM glucose. And in BMSCs cultured in osteogenic medium containing 25 mM glucose, the expression of these three osteoblastic genes was increased by 1.70, 1.53, and 1.48-fold, respectively (P < 0.05; Figure 4B(Fig. 4)), which was consistent with increase of BMP-2. Taken together, our results suggest that the BMP pathway plays an important role in regulating the osteogenic differentiation of BMSCs in a high-glucose environment.


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)

Up-regulated expression levels of RUNX2 by BMP-2 promoted BMSC osteogenic differentiation in normal (5.5 mM) and high-glucose (25 mM) conditions.A: The level of endogenic BMP-2 in BMSCs grown in basal osteogenic medium containing normal (5.5 mM) or high glucose (25 mM), or in the absence or presence of BMP-2 (100 ng/mL) for 7 d were measured by Western blot.B: Real-time PCR analysis of RUNX2, ALP, and OCN expression in BMSCs after 7-d culture in basal medium (Undiff) and osteogenic medium (Diff), containing normal (5.5 mM) or high glucose (25 mM) in the absence or presence of 100 ng/mL BMP-2. β-Actin was used as a control for equal loading. Results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal /Diff groups
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Up-regulated expression levels of RUNX2 by BMP-2 promoted BMSC osteogenic differentiation in normal (5.5 mM) and high-glucose (25 mM) conditions.A: The level of endogenic BMP-2 in BMSCs grown in basal osteogenic medium containing normal (5.5 mM) or high glucose (25 mM), or in the absence or presence of BMP-2 (100 ng/mL) for 7 d were measured by Western blot.B: Real-time PCR analysis of RUNX2, ALP, and OCN expression in BMSCs after 7-d culture in basal medium (Undiff) and osteogenic medium (Diff), containing normal (5.5 mM) or high glucose (25 mM) in the absence or presence of 100 ng/mL BMP-2. β-Actin was used as a control for equal loading. Results represent the mean ± SD from three independent experiments performed in triplicate. *P < 0.05 vs. the normal /Diff groups
Mentions: BMP-2 is known to positively regulate osteogenic differentiation. To verify whether treatment of BMSCs with BMP-2 can promote osteogenic differentiation and rescue the osteogenic suppression of high glucose, we tested the intracellular BMP-2 levels and RUNX2, ALP, and OCN expression in the BMSCs after treatment with ectogenic BMP-2. The intracellular BMP-2 in both osteogenic groups (5.5 mM and 25 mM glucose) was significantly elevated (Figure 4A(Fig. 4)). The expression of RUNX2, ALP, and OCN was also increased by 1.72, 1.47, and 1.47-fold in BMP-2-treated BMSCs cultured in osteogenic medium containing 5.5 mM glucose. And in BMSCs cultured in osteogenic medium containing 25 mM glucose, the expression of these three osteoblastic genes was increased by 1.70, 1.53, and 1.48-fold, respectively (P < 0.05; Figure 4B(Fig. 4)), which was consistent with increase of BMP-2. Taken together, our results suggest that the BMP pathway plays an important role in regulating the osteogenic differentiation of BMSCs in a high-glucose environment.

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