Immunohistochemical localization and mRNA expression of matrix Gla protein and fetuin-A in bone biopsies of hemodialysis patients.
Matrix Gla protein (MGP) and fetuin-A are inhibitors of arterial calcifications. In blood of rats, calcium-phosphate-fetuin-MGP complexes, produced in bone, have been identified. Indeed, an association between bone resorption, release of such complexes, and arterial calcifications has been reported. We have investigated the synthesis and localization of fetuin-A and MGP in bone of hemodialysis patients and the possible contribution of bone cells in arterial calcifications. Bone biopsies from 11 hemodialysis patients were used for histology, in situ hybridization of fetuin-A and MGP messenger RNA (mRNA), immunohistochemistry of fetuin-A, and total, carboxylated, and non-carboxylated MGP proteins. Patients showed various types of renal osteodystrophy, or normal bone. MGP was synthesized and expressed (total and carboxylated) by osteoblasts, osteocytes, and most osteoclasts, while fetuin-A by osteoblasts and osteocytes. Fetuin-A and carboxylated MGP proteins were positive in the calcified matrix, while total MGP was negative. Osteoid seams were negative to fetuin-A, lightly positive to carboxylated MGP, and occasionally positive to total MGP. Undercarboxylated MGP was mostly undetectable. In adult humans, fetuin-A is produced also by osteoblasts, and not only by hepatocytes, as previously believed. MGP, essentially carboxylated, is synthesized by osteoblasts and most osteoclasts. Increased bone turnover can be an important contributor to arterial calcifications.
Coen
Giorgio
G
Nephrology and Hypertension Unit, Ospedale Israelitico, Via Dandolo 75, 00153, Rome, Italy. giorgio.coen@gmail.com
Ballanti
Paola
P
Silvestrini
Giuliana
G
Mantella
Daniela
D
Manni
Micaela
M
Di Giulio
Salvatore
S
Pisanò
Stefania
S
Leopizzi
Martina
M
Di Lullo
Giuseppe
G
Bonucci
Ermanno
E
D000328:Adult; D000368:Aged; D001706:Biopsy; D001798:Blood Proteins / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D006435:Renal Dialysis / Q000009:adverse effects*; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein
D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein; C556354:AHSG protein, human