Limits...
Indoxyl sulfate promotes apoptosis in cultured osteoblast cells.

Kim YH, Kwak KA, Gil HW, Song HY, Hong SY - BMC Pharmacol Toxicol (2013)

Bottom Line: We found that IS increased caspase activity and induced apoptosis.The inhibition of OAT improved cell viability and suppressed the production of reactive oxygen species.These results suggest that IS is transported in MC3T3-E1 cells via OAT, which causes oxidative stress to inhibit osteoblast differentiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, 31 Soonchunhyang 6gil, Dongnam-gu, Cheonan, Chungnam 330-721, Korea. hwgil@schmc.ac.kr.

ABSTRACT

Background: Indoxyl sulfate (IS), an organic anion uremic toxin, promotes the progression of renal dysfunction. Some studies have suggested that IS inhibits osteoclast differentiation and suppresses parathyroid hormone (PTH)-stimulated intracellular cAMP production, decreases PTH receptor expression, and induces oxidative stress in primary mouse calvaria osteoblast cell culture. However, the direct effects of IS on osteoblast apoptosis have not been fully evaluated. Hence, we investigated whether IS acts as a bone toxin by studying whether IS induces apoptosis and inhibits differentiation in the cultured osteoblast cell line MC3T3-E1.

Methods: We assessed the direct effect of IS on osteoblast differentiation and apoptosis in the MC3T3-E1 cell line. We examined caspase-3/7 activity, apoptosis-related proteins, free radical production, alkaline phosphatase activity, and mRNA expression of type 1 collagen and osteonectin. Furthermore, we investigated the uptake of IS via organic anion transport (OAT).

Results: We found that IS increased caspase activity and induced apoptosis. Production of free radicals increased depending on the concentration of IS. Furthermore, IS inhibited the expression of mRNA type 1 collagen and osteonectin and alkaline phosphatase activity. The expression of OAT, which is known to mediate the cellular uptake of IS, was detected in in the MC3T3-E1 cell line. The inhibition of OAT improved cell viability and suppressed the production of reactive oxygen species. These results suggest that IS is transported in MC3T3-E1 cells via OAT, which causes oxidative stress to inhibit osteoblast differentiation.

Conclusions: IS acts as a bone toxin by inhibiting osteoblast differentiation and inducing apoptosis.

Show MeSH

Related in: MedlinePlus

Effect of IS on the viability of MC3T3-E1 cells. Cell number was measured 24 h after the addition of IS at concentrations ranging from 0.1 to 1.5 mM and was expressed as the percentage of control cells not pretreated with IS (open bar). The cell toxicity of IS was found to be dose dependent. The data represent the mean ± SEM from 8 replicates in each group. *P < 0.05 vs. control cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4222141&req=5

Figure 1: Effect of IS on the viability of MC3T3-E1 cells. Cell number was measured 24 h after the addition of IS at concentrations ranging from 0.1 to 1.5 mM and was expressed as the percentage of control cells not pretreated with IS (open bar). The cell toxicity of IS was found to be dose dependent. The data represent the mean ± SEM from 8 replicates in each group. *P < 0.05 vs. control cells.

Mentions: To determine cytotoxicity, the effect of IS on the cell proliferation of MC3E3-T1 was studied using an MTT assay. As shown in Figure 1, IS, at the concentration range of 0.1–1.5 mM, inhibited cell proliferation at 72 h.


Indoxyl sulfate promotes apoptosis in cultured osteoblast cells.

Kim YH, Kwak KA, Gil HW, Song HY, Hong SY - BMC Pharmacol Toxicol (2013)

Effect of IS on the viability of MC3T3-E1 cells. Cell number was measured 24 h after the addition of IS at concentrations ranging from 0.1 to 1.5 mM and was expressed as the percentage of control cells not pretreated with IS (open bar). The cell toxicity of IS was found to be dose dependent. The data represent the mean ± SEM from 8 replicates in each group. *P < 0.05 vs. control cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222141&req=5

Figure 1: Effect of IS on the viability of MC3T3-E1 cells. Cell number was measured 24 h after the addition of IS at concentrations ranging from 0.1 to 1.5 mM and was expressed as the percentage of control cells not pretreated with IS (open bar). The cell toxicity of IS was found to be dose dependent. The data represent the mean ± SEM from 8 replicates in each group. *P < 0.05 vs. control cells.
Mentions: To determine cytotoxicity, the effect of IS on the cell proliferation of MC3E3-T1 was studied using an MTT assay. As shown in Figure 1, IS, at the concentration range of 0.1–1.5 mM, inhibited cell proliferation at 72 h.

Bottom Line: We found that IS increased caspase activity and induced apoptosis.The inhibition of OAT improved cell viability and suppressed the production of reactive oxygen species.These results suggest that IS is transported in MC3T3-E1 cells via OAT, which causes oxidative stress to inhibit osteoblast differentiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, 31 Soonchunhyang 6gil, Dongnam-gu, Cheonan, Chungnam 330-721, Korea. hwgil@schmc.ac.kr.

ABSTRACT

Background: Indoxyl sulfate (IS), an organic anion uremic toxin, promotes the progression of renal dysfunction. Some studies have suggested that IS inhibits osteoclast differentiation and suppresses parathyroid hormone (PTH)-stimulated intracellular cAMP production, decreases PTH receptor expression, and induces oxidative stress in primary mouse calvaria osteoblast cell culture. However, the direct effects of IS on osteoblast apoptosis have not been fully evaluated. Hence, we investigated whether IS acts as a bone toxin by studying whether IS induces apoptosis and inhibits differentiation in the cultured osteoblast cell line MC3T3-E1.

Methods: We assessed the direct effect of IS on osteoblast differentiation and apoptosis in the MC3T3-E1 cell line. We examined caspase-3/7 activity, apoptosis-related proteins, free radical production, alkaline phosphatase activity, and mRNA expression of type 1 collagen and osteonectin. Furthermore, we investigated the uptake of IS via organic anion transport (OAT).

Results: We found that IS increased caspase activity and induced apoptosis. Production of free radicals increased depending on the concentration of IS. Furthermore, IS inhibited the expression of mRNA type 1 collagen and osteonectin and alkaline phosphatase activity. The expression of OAT, which is known to mediate the cellular uptake of IS, was detected in in the MC3T3-E1 cell line. The inhibition of OAT improved cell viability and suppressed the production of reactive oxygen species. These results suggest that IS is transported in MC3T3-E1 cells via OAT, which causes oxidative stress to inhibit osteoblast differentiation.

Conclusions: IS acts as a bone toxin by inhibiting osteoblast differentiation and inducing apoptosis.

Show MeSH
Related in: MedlinePlus