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Impaired osteocyte maturation in the pathogenesis of renal osteodystrophy.
Kidney Int. 2018 11; 94(5):1002-1012.KI

Abstract

Pediatric renal osteodystrophy is characterized by skeletal mineralization defects, but the role of osteoblast and osteocyte maturation in the pathogenesis of these defects is unknown. We evaluated markers of osteocyte maturation and programmed cell death in iliac crest biopsy samples from pediatric dialysis patients and healthy controls. We evaluated the relationship between numbers of fibroblast growth factor 23 (FGF23)-expressing osteocytes and histomorphometric parameters of skeletal mineralization. We confirmed that chronic kidney disease (CKD) causes intrinsic changes in bone cell maturation using an in vitro model of primary osteoblasts from patients with CKD and healthy controls. FGF23 co-localized with the early osteocyte marker E11/gp38, suggesting that FGF23 is a marker of early osteocyte maturation. Increased numbers of early osteocytes and decreased osteocyte apoptosis characterized CKD bone. Numbers of FGF23-expressing osteocytes were highest in patients with preserved skeletal mineralization indices, and packets of matrix surrounding FGF23-expressing osteocytes appeared to have entered secondary mineralization. Primary osteoblasts from patients with CKD retained impaired maturation and mineralization characteristics in vitro. Addition of FGF23 did not affect primary osteoblast mineralization. Thus, CKD is associated with intrinsic changes in osteoblast and osteocyte maturation, and FGF23 appears to mark a relatively early stage in osteocyte maturation. Improved control of renal osteodystrophy and FGF23 excess will require further investigation into the pathogenesis of CKD-mediated osteoblast and osteocyte maturation failure.

Authors+Show Affiliations

Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGK and AUVA Trauma Centre Meidling, 1(st) Medical Department, Hanusch Hospital, Vienna, Austria.Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGK and AUVA Trauma Centre Meidling, 1(st) Medical Department, Hanusch Hospital, Vienna, Austria.Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.School of Dentistry, UCLA, Los Angeles, California, USA.Department of Orthopedics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.Center for Molecular Oncology, UConn Health, Farmington, Connecticut, USA.Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGK and AUVA Trauma Centre Meidling, 1(st) Medical Department, Hanusch Hospital, Vienna, Austria.Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. Electronic address: kwesseling@mednet.ucla.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30348285

Citation

Pereira, Renata C., et al. "Impaired Osteocyte Maturation in the Pathogenesis of Renal Osteodystrophy." Kidney International, vol. 94, no. 5, 2018, pp. 1002-1012.
Pereira RC, Salusky IB, Roschger P, et al. Impaired osteocyte maturation in the pathogenesis of renal osteodystrophy. Kidney Int. 2018;94(5):1002-1012.
Pereira, R. C., Salusky, I. B., Roschger, P., Klaushofer, K., Yadin, O., Freymiller, E. G., Bowen, R., Delany, A. M., Fratzl-Zelman, N., & Wesseling-Perry, K. (2018). Impaired osteocyte maturation in the pathogenesis of renal osteodystrophy. Kidney International, 94(5), 1002-1012. https://doi.org/10.1016/j.kint.2018.08.011
Pereira RC, et al. Impaired Osteocyte Maturation in the Pathogenesis of Renal Osteodystrophy. Kidney Int. 2018;94(5):1002-1012. PubMed PMID: 30348285.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired osteocyte maturation in the pathogenesis of renal osteodystrophy. AU - Pereira,Renata C, AU - Salusky,Isidro B, AU - Roschger,Paul, AU - Klaushofer,Klaus, AU - Yadin,Ora, AU - Freymiller,Earl G, AU - Bowen,Richard, AU - Delany,Anne M, AU - Fratzl-Zelman,Nadja, AU - Wesseling-Perry,Katherine, PY - 2018/04/13/received PY - 2018/07/18/revised PY - 2018/08/09/accepted PY - 2018/10/24/entrez PY - 2018/10/24/pubmed PY - 2019/7/6/medline KW - FGF23 KW - apoptosis KW - mineralization KW - osteocyte KW - renal osteodystrophy SP - 1002 EP - 1012 JF - Kidney international JO - Kidney Int VL - 94 IS - 5 N2 - Pediatric renal osteodystrophy is characterized by skeletal mineralization defects, but the role of osteoblast and osteocyte maturation in the pathogenesis of these defects is unknown. We evaluated markers of osteocyte maturation and programmed cell death in iliac crest biopsy samples from pediatric dialysis patients and healthy controls. We evaluated the relationship between numbers of fibroblast growth factor 23 (FGF23)-expressing osteocytes and histomorphometric parameters of skeletal mineralization. We confirmed that chronic kidney disease (CKD) causes intrinsic changes in bone cell maturation using an in vitro model of primary osteoblasts from patients with CKD and healthy controls. FGF23 co-localized with the early osteocyte marker E11/gp38, suggesting that FGF23 is a marker of early osteocyte maturation. Increased numbers of early osteocytes and decreased osteocyte apoptosis characterized CKD bone. Numbers of FGF23-expressing osteocytes were highest in patients with preserved skeletal mineralization indices, and packets of matrix surrounding FGF23-expressing osteocytes appeared to have entered secondary mineralization. Primary osteoblasts from patients with CKD retained impaired maturation and mineralization characteristics in vitro. Addition of FGF23 did not affect primary osteoblast mineralization. Thus, CKD is associated with intrinsic changes in osteoblast and osteocyte maturation, and FGF23 appears to mark a relatively early stage in osteocyte maturation. Improved control of renal osteodystrophy and FGF23 excess will require further investigation into the pathogenesis of CKD-mediated osteoblast and osteocyte maturation failure. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/30348285/Impaired_osteocyte_maturation_in_the_pathogenesis_of_renal_osteodystrophy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(18)30592-1 DB - PRIME DP - Unbound Medicine ER -