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Published on: March 18, 2019
p-Cresyl sulfate induces osteoblast dysfunction through activating JNK and p38 MAPK pathways
Hisae Tanaka1, Yoshiko Iwasaki, Hideyuki Yamato
1Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Bone
|July 16, 2013
Summary
p-Cresyl sulfate (PCS) damages bone cells by increasing reactive oxygen species and activating specific cellular pathways, unlike indoxyl sulfate (IS). This finding is crucial for understanding bone abnormalities in chronic kidney disease.
Area of Science:
- Nephrology
- Bone Metabolism
- Cell Biology
Background:
- Uremic toxins are implicated in chronic kidney disease (CKD)-related bone abnormalities.
- p-Cresyl sulfate (PCS) is a significant uremic toxin linked to CKD progression and mortality.
- The specific impact of PCS on bone metabolism is not well understood.
Purpose of the Study:
- To investigate the toxic effects of PCS on primary mouse osteoblasts.
- To compare the mechanisms of PCS and indoxyl sulfate (IS) toxicity in osteoblasts.
Main Methods:
- Primary mouse osteoblasts were treated with varying concentrations of PCS and IS.
- Assays measured parathyroid hormone (PTH)-induced cAMP production, reactive oxygen species (ROS) generation, cell viability, and DNA fragmentation.
- Inhibition of JNK and p38 MAPK pathways was used to elucidate PCS mechanisms.
Main Results:
- PCS significantly reduced PTH-induced cAMP production and cell viability, while increasing DNA fragmentation and ROS production in a dose-dependent manner.
- PCS-induced osteoblast damage was mediated by ROS production and JNK/p38 MAPK activation.
- IS exhibited distinct toxicity profiles, requiring higher concentrations for similar effects and not impacting cAMP production.
Conclusions:
- PCS exerts toxic effects on osteoblasts through mechanisms involving ROS and JNK/p38 MAPK activation, differing from IS.
- These osteoblast damages induced by PCS may significantly contribute to impaired bone metabolism in CKD patients.
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