Osteoblast and Osteocyte Dysfunction in Chronic Kidney Disease

University Of California Los Angeles, Los Angeles CA

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Abstract

DESCRIPTION (provided by applicant): Osteocytes are key regulators of skeletal mineralization and their function is dysregulated in pediatric patients with chronic kidney disease, contributing to such adverse consequences including poor growth, boney deformities, bone pain and fractures. A more complete understanding of osteoblast/osteocyte biology and the process of skeletal mineralization is critical to improving skeletal outcomes. HYPOTHESIS: Osteoblasts harvested from CKD patients have intrinsic abnormalities in mineralization potential and these abnormalities are ameliorated and/or potentiated by changes in circulating hormone concentrations. METHODS: Paired samples of primary osteoblast cells from pediatric patients with stage V chronic kidney disease, obtained before and after active vitamin D sterol therapy, will be used to assess, in vitro, osteoblast maturation and mineralization characteristics and the effects of systemic vitamin D sterol therapy on these characteristics. Subsequently, alterations in mineral and hormonal content will be made to the cell culture media to evaluate the separate effects of these circulating factors on skeletal mineralization. IMPLICATIONS: The current study presents a novel system in which to study the pathophysiology of defective skeletal mineralization. Its advantages are the ability to discriminate whether defective mineralization is due to intrinsic changes in cells of osteoblast/osteocyte lineage, to alterations in extrinsic factrs (changes in media mineral and hormone content), or to a combination of both. These results will yield considerable knowledge which can, in future, be used to develop new therapeutic strategies for the treatment of renal osteodystrophy.