Transcriptomics: a Solution for Renal Osteodystrophy?
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KIDNEY AND BONE (IB SALUSKY AND T NICKOLAS, SECTION EDITORS)
Transcriptomics: a Solution for Renal Osteodystrophy? Aline Martin 1 & Valentin David 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review The molecular mechanisms of the bone disease associated with chronic kidney disease (CKD), called renal osteodystrophy (ROD), are poorly understood. New transcriptomics technologies may provide clinically relevant insights into the pathogenesis of ROD. This review summarizes current progress and limitations in the study and treatment of ROD, and in transcriptomics analyses of skeletal tissues. Recent Findings ROD is characterized by poor bone quality and strength leading to increased risk of fracture. Recent studies indicate permanent alterations in bone cell populations during ROD. Single-cell transcriptomics analyses, successful at identifying specialized cell subpopulations in bone, have not yet been performed in ROD. Summary ROD is a widespread poorly understood bone disease with limited treatment options. Transcriptomics analyses of bone are needed to identify the bone cell subtypes and their role in the pathogenesis of ROD, and to develop adequate diagnosis and treatment strategies. Keywords Renal osteodystrophy . Bone and mineral metabolism . Chronic kidney disease . Transcriptomics . Bulk RNA sequencing . Single-cell RNA sequencing
Introduction Chronic kidney disease (CKD) is associated with major disturbances in mineral and bone metabolism, defined as CKDmineral and bone disorder (CKD-MBD). Renal osteodystrophy (ROD) is the skeletal component of CKDMBD that corresponds to alterations in bone metabolism, including impaired bone mineralization and impaired bone remodeling, leading to changes in bone morphology. These translate into poor bone quality and strength and severely increased risk of fractures in all patients with end stage kidney disease (ESKD). Despite alarming statistics, the pathology of ROD remains poorly understood, and effective strategies for
This article is part of the Topical Collection on Kidney and Bone * Aline Martin [email protected] * Valentin David [email protected] 1
Division of Nephrology and Hypertension, Center for Translational Metabolism and Health and Feinberg Cardiovascular and Renal Research Institute, Northwestern University, 320 East Superior Street, Chicago, IL 60611, USA
the treatment of ROD, designed to improve bone health and prevent fractures, are lacking. The critical barrier to understanding ROD originates from the multifactorial nature of the disease and the lack of adequate tools to study the underlying cellular and molecular mechanisms of onset and progression of ROD. Similar to osteoporosis, the current diagnostic of ROD relies on the measure of circulating markers of bone and mineral metabolism a n d o n a na l y s es of b o n e d en s i t y, bo n e v o l u m e , microarchitecture and remodeling using skeletal X-ray imaging, and bone biopsies. However, anabolic and antiresorptive agents c
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