title: Osteocytic protein expression response to doxercalciferol therapy in pediatric dialysis patients.
abstract: BACKGROUND
  Osteocytic protein expression is dysregulated in CKD and is affected by changes in mineral metabolism; however the effects of active vitamin D sterol therapy on osteocyte protein expression in advanced CKD is unknown.
  
  
  METHODS
  Eleven pediatric patients with end stage kidney disease underwent bone biopsy, were treated for 8 months with doxercalciferol, and then underwent a second bone biopsy. Bone expression of fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP1), and sclerostin were determined by immunohistochemistry and quantified by Ariol Scanning. Western blot analysis and qRT-PCR was performed on bone abstracts of a subset of study subjects to determine the nature (i.e. size) of FGF23 and DMP1 in bone before and after therapy.
  
  
  RESULTS
  As assessed by immunohistochemistry, bone FGF23, DMP1 and sclerostin protein all increased with therapy. In the case of FGF23, this increase was due to an increase in the full-length molecule without the appearance of FGF23 fragments. DMP1 was present primarily in its full-length form in healthy controls while 57kDa and 37kDa fragments of DMP1 were apparent in bone of dialysis patients at baseline and the 57 kDa appeared to decrease with therapy.
  
  
  CONCLUSIONS
  Marked changes in osteocytic protein expression accompany doxercalciferol therapy, potentially impacting bone mineralization and the skeletal response to PTH. The effects of these bone changes on long-term outcomes remain to be determined.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors.forename: Renata C
authors.initials: RC
authors.lastname: Pereira
authors.affiliation: Endocrine Unit and Pediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gales
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors.forename: Isidro B
authors.initials: IB
authors.lastname: Salusky
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Wesseling-Perry
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D001706:Biopsy; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D010011:Osteocytes / Q000378:metabolism; D010014:Osteolysis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; C513309:DMP1 protein, human; D004872:Ergocalciferols; D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; D005819:Genetic Markers; D010750:Phosphoproteins; C422903:SOST protein, human; C042533:1 alpha-hydroxyergocalciferol; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23