Patients with chronic kidney disease (CKD) develop various bone abnormalities characterized by impaired bone remodelling. Recent data suggest that accumulation of the uraemic toxin indoxyl sulphate (IS) may be one of the factors involved in bone abnormalities in CKD patients. Indeed, it was recently reported that IS induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells. However, it is not yet known whether IS also affects osteoclast cells.
In the present study, we assessed the direct effect of IS at uraemic concentrations and in the presence (to reach the 3 mM concentration) or absence of added inorganic phosphate (Pi) on osteoclast (OCL) differentiation and bone-resorbing activity in two well-established cellular models of monocyte/macrophage (peripheral blood mononuclear cells and the RAW 264.7 cell line).
We found that IS inhibits both OCL differentiation and bone-resorbing activity in a dose-dependent manner and that these effects were enhanced in the presence of Pi at 3mM concentration. IS induced a gradual inhibition of JNK, Akt, p38, ERK1/2 phosphorylation and AP-1 DNA-binding activity. The effects of IS on OCL differentiation and AP-1 were prevented by probenecid, a competitive inhibitor of organic anion transporters, suggesting that IS's effects occur subsequently to its intake.
Our findings strongly suggest that IS not only inhibits osteoblast function but also has an inhibitory effect on OCL function and thus could affect bone remodelling in CKD patients.
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"3. Results 3.1. Pi induces a marked decrease of osteoclastogenesis in RAW cells which is related to concomitant decrease of miR-223 levels Our group previously reported that 3 mM Pi, a concentration found in CKD patients, decreases osteoclastic differentiation  . This finding was confirmed in the present study (Fig. 1A). "
[Show abstract][Hide abstract]ABSTRACT: Reviews all the latest basic and clinical research findings. With contributions from leading international experts in the field, this book is dedicated to all facets of uremic toxins research, including low molecular weight solutes, protein-bound solutes, and middle molecules. Moreover, it covers everything from basic mass spectrometry research to the latest clinical findings and practices. Uremic Toxins is divided into three sections: Section One, Uremic Toxins, explores the definition, classification, listing, and mass spectrometric analysis of uremic toxins. Section Two, Selected Uremic Toxins, describes key uremic toxins, explaining chemical structures, metabolism, analytical methods, plasma levels, toxicity, clinical implications, and removal methods. Among the uremic toxins covered are indoxyl sulfate, asymmetric dimethylarginine, PTH, β2-microglobulin, and AGEs. Section Three, Therapeutic Removal of Uremic Toxins, describes how uremic toxins can be removed by hemodialysis, peritoneal dialysis, and oral sorbent. All chapters are based on the authors' thorough review of the literature as well as their own personal laboratory and clinical experience. References at the end of each chapter provide a gateway to the literature in the field. Reviewing all the latest basic and clinical research findings, Uremic Toxins will help bench scientists in nephrology advance their own investigations. It will also help clinicians take advantage of the latest tested and proven treatments for the management of chronic kidney disease.
[Show abstract][Hide abstract]ABSTRACT: The Copenhagen 2012 Nexus symposium on 'Bone and the Kidney' followed the 'bench to bedside' approach of the Nexus symposia organized by the International Society of Nephrology. The main goal of the present symposium was to provide a unique forum for scientists and clinicians with an interest in the fascinating world of the many hormones and factors involved in mineral homeostasis, bone disease, and vascular calcification of patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). The possibility of exchanging cutting-edge insights and discussing clinically relevant information on all aspects of the bone-kidney axis was open to all participants. The numerous lectures given at the symposium addressed current knowledge and recent advances in kidney and bone physiology, as well as the pathogenesis, diagnosis, and therapy of CKD-MBD, inspired by the intention to enhance the translation of basic science into clinical medicine. The lectures were followed by lively discussions of open questions and controversial issues. Our brief summary of interesting novel findings presented at this symposium is necessarily the result of a somewhat arbitrary choice among a wealth of exciting data brought to the attention of an enthusiastic audience.Kidney International advance online publication, 16 January 2013; doi:10.1038/ki.2012.453.
No preview · Article · Jan 2013 · Kidney International