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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

Primer sequences used in real-time RT-PCR
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T1: Primer sequences used in real-time RT-PCR

Mentions: Cells were cultured and divided into four groups as above. Total RNA was isolated using TRIzol (Invitrogen) at day seven. Approximately 2-5 µg total RNA from each group was converted to cDNA with a SuperScript First-Strand Synthesis kit (Invitrogen). The quantitative real-time polymerase chain reaction (qRT-PCR) was performed using a QuantiTect SYBR Green PCR kit (Toyobo, Osaka, Japan) and the Applied Biosystems 7500 Real-time PCR Detection System (Applied Biosystems, Foster City, CA, USA). Two independent experiments were performed for each reaction in triplicate. The primers used are listed in Table 1(Tab. 1).


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)

Primer sequences used in real-time RT-PCR
© Copyright Policy - open-access
Related In: Results  -  Collection

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

T1: Primer sequences used in real-time RT-PCR
Mentions: Cells were cultured and divided into four groups as above. Total RNA was isolated using TRIzol (Invitrogen) at day seven. Approximately 2-5 µg total RNA from each group was converted to cDNA with a SuperScript First-Strand Synthesis kit (Invitrogen). The quantitative real-time polymerase chain reaction (qRT-PCR) was performed using a QuantiTect SYBR Green PCR kit (Toyobo, Osaka, Japan) and the Applied Biosystems 7500 Real-time PCR Detection System (Applied Biosystems, Foster City, CA, USA). Two independent experiments were performed for each reaction in triplicate. The primers used are listed in Table 1(Tab. 1).

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