Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation

PLoS One. 2015 Sep 21;10(9):e0138156. doi: 10.1371/journal.pone.0138156. eCollection 2015.

Abstract

Background: Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function.

Methods: Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies.

Results: FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01).

Conclusions: Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Bone Morphogenetic Proteins / analysis*
  • Bone and Bones / metabolism
  • Bone and Bones / pathology*
  • Child
  • Cross-Sectional Studies
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / analysis*
  • Genetic Markers
  • Heart Transplantation* / adverse effects
  • Humans
  • Kidney Transplantation* / adverse effects
  • Liver Transplantation* / adverse effects
  • Male
  • Osteocytes / metabolism
  • Osteocytes / pathology*
  • Renal Insufficiency, Chronic / complications
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Proteins
  • FGF23 protein, human
  • Genetic Markers
  • SOST protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23