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High glucose inhibits receptor activator of nuclear factor‑κB ligand-induced osteoclast differentiation via downregulation of v‑ATPase V0 subunit d2 and dendritic cell‑specific transmembrane protein.

Xu J, Yue F, Wang J, Chen L, Qi W - Mol Med Rep (2014)

Bottom Line: The expression levels of Atp6V0d2 and DC‑STAMP are regulated by NFATc1 and c‑fos, and are required for osteoclast fusion, which is important for osteoclast maturation.To the best of our knowledge, the present study demonstrated for the first time that high glucose decreased the gene expression of ATP6v0d2 and DC‑STAMP in RAW264.7 cells mediated by RANKL.Therefore, the suppression of pre‑osteoclast or osteoclast fusion may be essential for the inhibition of osteoclast differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

ABSTRACT
The balance between bone formation and resorption is compromised in diabetes, which may contribute to the high risk of fractures in diabetic patients. However, the mechanism by which high glucose affects bone turnover remains to be elucidated. The present study demonstrated that high glucose inhibited receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclastogenesis. In order to examine the mechanism involved in the inhibition of osteoclastogenesis, the present study examined several key molecules involved in osteoclast differentiation, including v‑ATPase V0 subunit d2 (Atp6V0d2), dendritic cell‑specific transmembrane protein (DC-STAMP), c‑fos and nuclear factor of activated T cells c1 (NFATc1). The expression levels of Atp6V0d2 and DC‑STAMP are regulated by NFATc1 and c‑fos, and are required for osteoclast fusion, which is important for osteoclast maturation. To the best of our knowledge, the present study demonstrated for the first time that high glucose decreased the gene expression of ATP6v0d2 and DC‑STAMP in RAW264.7 cells mediated by RANKL. Therefore, the suppression of pre‑osteoclast or osteoclast fusion may be essential for the inhibition of osteoclast differentiation.

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Effect of high glucose on the mRNA expression levels of c-fos and NFATc1. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates and cultured with RANKL and different doses (5.6 and 20.2 mM) of D-glucose or mannitol for 5 days. The mRNA expression levels of (A) c-fos and (B) NFATc1 were analyzed using reverse transcription-quantitative polymerase chain reaction. Data are expressed as the mean ± standard deviation of the quantification of target expression relative to the untreated group following normalization against β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). *P<0.05 and **P<0.01 vs 5.6 mM glucose-treated cells. RANKL, receptor activator of nuclear factor-κB ligand; NFATc1, nuclear factor of activated T cells c1.
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f3-mmr-11-02-0865: Effect of high glucose on the mRNA expression levels of c-fos and NFATc1. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates and cultured with RANKL and different doses (5.6 and 20.2 mM) of D-glucose or mannitol for 5 days. The mRNA expression levels of (A) c-fos and (B) NFATc1 were analyzed using reverse transcription-quantitative polymerase chain reaction. Data are expressed as the mean ± standard deviation of the quantification of target expression relative to the untreated group following normalization against β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). *P<0.05 and **P<0.01 vs 5.6 mM glucose-treated cells. RANKL, receptor activator of nuclear factor-κB ligand; NFATc1, nuclear factor of activated T cells c1.

Mentions: RANKL induces the expression of c-Fos and NFATc1 in osteoclastogenesis (25–27) and the transcriptional induction of NFATc1 is a major function of c-Fos in osteoclast differentiation (28). The present study examined the effects of high glucose on the gene expression of c-fos and NFATc1 through RT-qPCR. The addition of high glucose to RAW 264.7 cells cultured in the presence of RANKL downregulated the gene expression of c-fos 2.0-fold (P<0.05) and NFATc1 1.7-fold (P<0.01) as shown in Fig. 3, however, no affect was observed in the gene expression of c-fos or NFATc1 in the cultures incubated with mannitol (P>0.05).


High glucose inhibits receptor activator of nuclear factor‑κB ligand-induced osteoclast differentiation via downregulation of v‑ATPase V0 subunit d2 and dendritic cell‑specific transmembrane protein.

Xu J, Yue F, Wang J, Chen L, Qi W - Mol Med Rep (2014)

Effect of high glucose on the mRNA expression levels of c-fos and NFATc1. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates and cultured with RANKL and different doses (5.6 and 20.2 mM) of D-glucose or mannitol for 5 days. The mRNA expression levels of (A) c-fos and (B) NFATc1 were analyzed using reverse transcription-quantitative polymerase chain reaction. Data are expressed as the mean ± standard deviation of the quantification of target expression relative to the untreated group following normalization against β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). *P<0.05 and **P<0.01 vs 5.6 mM glucose-treated cells. RANKL, receptor activator of nuclear factor-κB ligand; NFATc1, nuclear factor of activated T cells c1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262508&req=5

f3-mmr-11-02-0865: Effect of high glucose on the mRNA expression levels of c-fos and NFATc1. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates and cultured with RANKL and different doses (5.6 and 20.2 mM) of D-glucose or mannitol for 5 days. The mRNA expression levels of (A) c-fos and (B) NFATc1 were analyzed using reverse transcription-quantitative polymerase chain reaction. Data are expressed as the mean ± standard deviation of the quantification of target expression relative to the untreated group following normalization against β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). *P<0.05 and **P<0.01 vs 5.6 mM glucose-treated cells. RANKL, receptor activator of nuclear factor-κB ligand; NFATc1, nuclear factor of activated T cells c1.
Mentions: RANKL induces the expression of c-Fos and NFATc1 in osteoclastogenesis (25–27) and the transcriptional induction of NFATc1 is a major function of c-Fos in osteoclast differentiation (28). The present study examined the effects of high glucose on the gene expression of c-fos and NFATc1 through RT-qPCR. The addition of high glucose to RAW 264.7 cells cultured in the presence of RANKL downregulated the gene expression of c-fos 2.0-fold (P<0.05) and NFATc1 1.7-fold (P<0.01) as shown in Fig. 3, however, no affect was observed in the gene expression of c-fos or NFATc1 in the cultures incubated with mannitol (P>0.05).

Bottom Line: The expression levels of Atp6V0d2 and DC‑STAMP are regulated by NFATc1 and c‑fos, and are required for osteoclast fusion, which is important for osteoclast maturation.To the best of our knowledge, the present study demonstrated for the first time that high glucose decreased the gene expression of ATP6v0d2 and DC‑STAMP in RAW264.7 cells mediated by RANKL.Therefore, the suppression of pre‑osteoclast or osteoclast fusion may be essential for the inhibition of osteoclast differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

ABSTRACT
The balance between bone formation and resorption is compromised in diabetes, which may contribute to the high risk of fractures in diabetic patients. However, the mechanism by which high glucose affects bone turnover remains to be elucidated. The present study demonstrated that high glucose inhibited receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclastogenesis. In order to examine the mechanism involved in the inhibition of osteoclastogenesis, the present study examined several key molecules involved in osteoclast differentiation, including v‑ATPase V0 subunit d2 (Atp6V0d2), dendritic cell‑specific transmembrane protein (DC-STAMP), c‑fos and nuclear factor of activated T cells c1 (NFATc1). The expression levels of Atp6V0d2 and DC‑STAMP are regulated by NFATc1 and c‑fos, and are required for osteoclast fusion, which is important for osteoclast maturation. To the best of our knowledge, the present study demonstrated for the first time that high glucose decreased the gene expression of ATP6v0d2 and DC‑STAMP in RAW264.7 cells mediated by RANKL. Therefore, the suppression of pre‑osteoclast or osteoclast fusion may be essential for the inhibition of osteoclast differentiation.

Show MeSH
Related in: MedlinePlus