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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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Related in: MedlinePlus

Effect of high glucose on the mRNA expression levels of ATP6v0d2 and DC-STAMP. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates cultured with RANKL and different doses of D-glucose (5.6 and 20.2 mM) or mannitol for 5 days. The mRNA expression levels of (A) ATP6v0d2 and (B) DC-STAMP 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 the expression of β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). **P<0.01, vs. 5.6 mM glucose-treated cells. Atp6v0d2, v-ATPase V0 subunit d2; DC-STAMP, dendritic cell-specific transmembrane protein; RANKL, receptor activator of nuclear factor-κB ligand.
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f4-mmr-11-02-0865: Effect of high glucose on the mRNA expression levels of ATP6v0d2 and DC-STAMP. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates cultured with RANKL and different doses of D-glucose (5.6 and 20.2 mM) or mannitol for 5 days. The mRNA expression levels of (A) ATP6v0d2 and (B) DC-STAMP 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 the expression of β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). **P<0.01, vs. 5.6 mM glucose-treated cells. Atp6v0d2, v-ATPase V0 subunit d2; DC-STAMP, dendritic cell-specific transmembrane protein; RANKL, receptor activator of nuclear factor-κB ligand.


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 ATP6v0d2 and DC-STAMP. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates cultured with RANKL and different doses of D-glucose (5.6 and 20.2 mM) or mannitol for 5 days. The mRNA expression levels of (A) ATP6v0d2 and (B) DC-STAMP 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 the expression of β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). **P<0.01, vs. 5.6 mM glucose-treated cells. Atp6v0d2, v-ATPase V0 subunit d2; DC-STAMP, dendritic cell-specific transmembrane protein; RANKL, receptor activator of nuclear factor-κB ligand.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-mmr-11-02-0865: Effect of high glucose on the mRNA expression levels of ATP6v0d2 and DC-STAMP. RAW264.7 cells were seeded at a density of 1×105 cells/well in 6-well plates cultured with RANKL and different doses of D-glucose (5.6 and 20.2 mM) or mannitol for 5 days. The mRNA expression levels of (A) ATP6v0d2 and (B) DC-STAMP 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 the expression of β-actin (2−ΔΔCt method). The untreated group were defined as the standard (=1). **P<0.01, vs. 5.6 mM glucose-treated cells. Atp6v0d2, v-ATPase V0 subunit d2; DC-STAMP, dendritic cell-specific transmembrane protein; RANKL, receptor activator of nuclear factor-κB ligand.
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