Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease.
Fibroblast growth factor 23 (FGF-23), dentin matrix protein 1 (DMP1), and matrix extracellular phosphoglycoprotein (MEPE) are skeletal proteins involved in the regulation of phosphate homeostasis and bone metabolism. Circulating FGF-23 levels are increased in patients with chronic kidney disease (CKD); however, FGF-23 skeletal expression and its regulation by DMP1 and MEPE have yet to be evaluated. Thus, expression of these three proteins was characterized by immunohistochemistry in 32 pediatric and young adult patients with CKD stages 2-5. When compared to normal controls, bone FGF-23 and DMP1 expression were increased in all stages of CKD; significant differences in bone FGF-23 and DMP1 expression were not detected between pre-dialysis CKD and dialysis patients. Bone MEPE expression in CKD did not differ from controls. FGF-23 was expressed in osteocyte cell bodies located at the trabecular periphery. DMP1 was widely expressed in osteocyte cell bodies and dendrites throughout bone. MEPE was also expressed throughout bone, but only in osteocyte cell bodies. Bone FGF-23 expression correlated directly with plasma levels of the protein (r=0.43, p<0.01) and with bone DMP1 expression (r=0.54, p<0.01) and expression of both proteins were inversely related to osteoid accumulation. Bone MEPE expression was inversely related to bone volume. In conclusion, skeletal FGF-23 and DMP1 expression are increased in CKD and are related to skeletal mineralization. The patterns of expression of FGF-23, MEPE, and DMP1 differ markedly in trabecular bone, suggesting that individual osteocytes may have specialized functions. Increases in bone FGF-23 and DMP1 expression suggest that osteocyte function is altered early in the course of CKD.
Pereira
Renata C
RC
Department of Pediatrics, David Geffen School of Medicine at UCLA, A2-383 MDCC, 650 Charles Young Drive East, Los Angeles, CA 90095, USA.
Juppner
Harald
H
Azucena-Serrano
Carlos E
CE
Yadin
Ora
O
Salusky
Isidro B
IB
Wesseling-Perry
Katherine
K
D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003710:Demography; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism*; D013194:Staining and Labeling; D055815:Young Adult
C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; D006023:Glycoproteins; C486579:MEPE protein, human; D010750:Phosphoproteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
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