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Impaired osteocyte maturation in the pathogenesis of renal osteodystrophy
- Source :
- Kidney International. 94:1002-1012
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
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.
- Subjects :
- Adult
Male
0301 basic medicine
Fibroblast growth factor 23
Programmed cell death
medicine.medical_specialty
Adolescent
Apoptosis
030209 endocrinology & metabolism
urologic and male genital diseases
Osteocytes
Article
Pathogenesis
Young Adult
03 medical and health sciences
0302 clinical medicine
Internal medicine
Bone cell
medicine
Humans
Renal osteodystrophy
Renal Insufficiency, Chronic
Child
Chronic Kidney Disease-Mineral and Bone Disorder
Osteoblasts
business.industry
Osteoblast
medicine.disease
Fibroblast Growth Factors
Fibroblast Growth Factor-23
stomatognathic diseases
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Nephrology
Child, Preschool
Osteocyte
Female
business
Kidney disease
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....49d94e444449c7ec828b1a3844347f94