title: Primary osteoblast-like cells from patients with end-stage kidney disease reflect gene expression, proliferation, and mineralization characteristics ex vivo.
abstract: Osteocytes regulate bone turnover and mineralization in chronic kidney disease. As osteocytes are derived from osteoblasts, alterations in osteoblast function may regulate osteoblast maturation, osteocytic transition, bone turnover, and skeletal mineralization. Thus, primary osteoblast-like cells were cultured from bone chips obtained from 24 pediatric ESKD patients. RNA expression in cultured cells was compared with RNA expression in cells from healthy individuals, to RNA expression in the bone core itself, and to parameters of bone histomorphometry. Proliferation and mineralization rates of patient cells were compared with rates in healthy control cells. Associations were observed between bone osteoid accumulation, as assessed by bone histomorphometry, and bone core RNA expression of osterix, matrix gla protein, parathyroid hormone receptor 1, and RANKL. Gene expression of osteoblast markers was increased in cells from ESKD patients and signaling genes including Cyp24A1, Cyp27B1, VDR, and NHERF1 correlated between cells and bone cores. Cells from patients with high turnover renal osteodystrophy proliferated more rapidly and mineralized more slowly than did cells from healthy controls. Thus, primary osteoblasts obtained from patients with ESKD retain changes in gene expression ex vivo that are also observed in bone core specimens. Evaluation of these cells in vitro may provide further insights into the abnormal bone biology that persists, despite current therapies, in patients with ESKD.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Renata C
authors.initials: RC
authors.lastname: Pereira
authors.affiliation: Center for Molecular Medicine, University of Connecticut Health Center, Los Angeles, California, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Delany
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Khouzam
authors.affiliation: Department of Orthopedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Bowen
authors.affiliation: UCLA School of Dentistry, Los Angeles, California, USA.
authors.forename: Earl G
authors.initials: EG
authors.lastname: Freymiller
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Isidro B
authors.initials: IB
authors.lastname: Salusky
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Wesseling-Perry
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000293:Adolescent; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology*; D002113:Calcification, Physiologic; D002135:Calcium-Binding Proteins / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology; D008297:Male; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics; D053245:RANK Ligand / Q000235:genetics; D012313:RNA / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics; D000097568:Matrix Gla Protein
chemical_list: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D053245:RANK Ligand; D012313:RNA; D044168:Receptor, Parathyroid Hormone, Type 1; D018167:Receptors, Calcitriol; D017923:Sodium-Hydrogen Exchangers; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors; D065668:Vitamin D3 24-Hydroxylase; D000097568:Matrix Gla Protein; C478163:SP7 protein, human; C505688:TNFSF11 protein, human; C579457:VDR protein, human; C093376:sodium-hydrogen exchanger regulatory factor; C585549:CYP24A1 protein, human; C000600378:CYP27B1 protein, human