Abstract: FR-PO503
Primary CKD Osteoblasts Are Resistant to the Pro-Maturation Effects of 1,25D In Vitro
Session Information
- Bone and Mineral Metabolism: Basic
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 401 Bone and Mineral Metabolism: Basic
Authors
- Pereira, Renata C., University of California, Los Angeles, California, United States
- Salusky, Isidro B., Mattel Children's Hospital, Los Angeles, California, United States
- Delany, Anne M., University of Connecticut Health Center, Farmington, Connecticut, United States
- Wesseling-Perry, Katherine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
Background
Osteoblast maturation and bone mineralization are integrally linked processes. Pediatric CKD patients have a high prevalence of skeletal mineralization defects in vivo and primary CKD osteoblasts demonstrate intrinsic impairments in maturation in vitro. 1,25D simultaneously stimulates osteoblast maturation and bone FGF23 expression while overexpression of FGF23 in primary rodent osteoblasts impairs their maturation and mineralization. However, the independent effects of 1,25D and FGF23 on osteoblast differentiation in CKD are unknown.
Methods
To investigate this, primary osteoblasts from 6 adolescent dialysis patients and 3 healthy adolescent controls were grown to confluence and stimulated to mineralize in differentiation media for 2 weeks. Mineralization was quantified by staining cultures with 1% Alizarin Red S; gene expression was evaluated by qPCR in parallel cultures.
Results
Mineralization was greater in healthy control than in CKD osteoblasts. 1,25D increased mineralization of CKD osteoblasts (Fig A). FGF23 did not affect mineralization in either CKD or healthy control cultures (Fig B). Runx2 (early osteoblast marker) expression was similar in healthy control and CKD osteoblasts at baseline and increased in both groups with time. 1,25D increased Runx2 in control, but not CKD, osteoblasts (Fig C). Osteocalcin (Bglap) (mature osteoblast marker) expression was higher in control than in CKD osteoblasts at baseline. 1,25D stimulated Bglap in both groups (Fig D). FGF23 did not affect Runx2 or Bglap.
Conclusion
These data suggest that CKD osteoblasts are resistant to the pro-maturation effects of 1,25D. This 1,25D resistance may contribute to the mineralization defects that persist in pediatric CKD patients despite current renal osteodystrophy therapies. The mechanism behind CKD osteoblast maturation resistance, which appears unrelated to exogenous FGF23, requires further evaluation.
Figure
Funding
- Other NIH Support