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. 2009 Dec;45(6):1161-8.
doi: 10.1016/j.bone.2009.08.008. Epub 2009 Aug 11.

Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease

Renata C Pereira  1 , Harald Juppner, Carlos E Azucena-Serrano, Ora Yadin, Isidro B Salusky, Katherine Wesseling-Perry
Affiliations

Patterns of FGF-23, DMP1, and MEPE expression in patients with chronic kidney disease

Renata C Pereira et al. Bone. 2009 Dec.

Erratum in

Abstract

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.

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Figures

Figure 1
Figure 1
Staining of FGF-23 in cancellous bone. Arrows indicate osteoctyes with positive staining. Trabeculae and bone marrow are labeled TB and BM respectively. A. Normal control (50x). B. Normal control (200x). C. Adolescent girl with CKD stage 2 (GFR:71; Ca:10.2; P: 4.5; Alk Phos:265; PTH:12; intact FGF-23:166; C-terminal FGF-23:462; 25(OH)D:25 (50x). D: CKD stage 2 (200x). Bone FGF-23 expression was 1.21/mm2.
Figure 2
Figure 2
Staining of DMP1 in cancellous bone under 50x and 200x magnification. Arrows indicate osteoctyes with positive staining. Trabeculae and bone marrow are labeled TB and BM respectively. A. Normal control (50x). B. Normal control (200x). C. CKD stage 2 (50x). D: CKD stage 2 (200x). Bone DMP1 expression was 0.35/mm2.
Figure 3
Figure 3
Staining of MEPE in cancellous bone under 50x and 200x magnification. Arrows indicate osteoctyes with positive staining. Trabeculae and bone marrow are labeled TB and BM respectively. A. Normal control (50x). B. Normal control (200x). C. CKD stage 2 (50x). D: CKD stage 2 (200x). Bone MEPE expression was 7.94/mm2.
See this image and copyright information in PMC

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