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Abstract: FR-PO502

Vitamin D Increases Bone FGF23 Expression by Increasing Numbers of Early Osteocytes

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Pereira, Renata C., University of California, Los Angeles, California, United States
  • Noche, Kathleen, UCLA, Los Angeles, California, United States
  • Gales, Barbara, University of California Los Angeles, Los Angeles, California, United States
  • Salusky, Isidro B., Mattel Children's Hospital, Los Angeles, California, United States
  • Wesseling-Perry, Katherine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
Background

Vitamin D directly stimulates osteoblast maturation and FGF23 expression. FGF23 is expressed in early osteocytes at the trabecular periphery. Whether the vitamin D-mediated increase in bone FGF23 expression reflects increased numbers of early osteocytes or an increase in per-osteocyte expression is unknown.

Methods

We evaluated markers of osteocyte maturity and FGF23 expression by immunohistochemistry (IH) and immunofluorescence (IF) and osteocyte apoptosis by TUNEL staining in iliac crest of 11 dialysis pts age 15.8+0.8 years who underwent bone biopsy before and after 8 mos of doxercalciferol (D) therapy. Bone protein expression was evaluated by Ariol scanning of IH. Numbers of FGF23-expressing osteocytes were counted and normalized by bone area. RNA was extracted from cores and evaluated by qRT-PCR.

Results

FGF23 co-localized with e11/gp38, a marker of early osteocytes (Fig 1A). Numbers of FGF23-expressing osteocytes correlated with FGF23 protein expression (r=0.83, p<0.001). Numbers of FGF23-expressing osteocytes increased by 226 (83, 440)% and FGF23 mRNA increased by 226 (124, 320)% in response to D. Expression of sclerostin, a mature osteocyte marker, increased in cortical bone in response to D (p<0.05). Osteocyte apoptosis was low at baseline but increased with D (Fig 1B).

Conclusion

The co-localization of FGF23 with e11/gp38 suggests that increased numbers of FGF23-expressing osteocytes reflect a D-mediated increase in early osteocytes. The tight relationships between FGF23 RNA message, FGF23 protein, and numbers of FGF23-expressing osteocytes suggest that D-mediated increases in FGF23 expression are due to increased numbers of FGF23-expressing osteocytes in CKD bone. Increased osteocyte apoptosis suggests that D is associated with increased osteocyte turnover. Further studies into altered osteocyte maturation, the effects of medications on osteocyte biology, and their implications for clinical bone disease in CKD patients are warranted.

Figure 1

Funding

  • Other NIH Support