bone impairment in phenylketonuria is characterized by circulating osteoclast precursors and activated t cell increase骨损伤在苯丙酮尿症的特征是循环破骨细胞前体和激活t细胞增加.pdfVIP

Bone Impairment in Phenylketonuria Is Characterized by Circulating Osteoclast Precursors and Activated T Cell Increase 1 . 2. 2 1 2 2 Ilaria Roato * , Francesco Porta , Alessandro Mussa , Lucia D’Amico , Ludovica Fiore , Davide Garelli , Marco Spada2, Riccardo Ferracini1,2,3 1 Center for Experimental Research and Medical Studies, A.O.U. San Giovanni Battista, Torino, Italy, 2 Department of Pediatrics, University of Torino, Torino, Italy, 3 Department of Orthopaedics, A.O.U. San Giovanni Battista, Torino, Italy Abstract Background: Phenylketonuria (PKU) is a rare inborn error of metabolism often complicated by a progressive bone impairment of uncertain etiology, as documented by both ionizing and non- ionizing techniques. Methodology: Peripheral blood mononuclear cell (PBMC) cultures were performed to study osteoclastogenesis, in the presence or absence of recombinant human monocyte-colony stimulating factor (M-CSF) and receptor activator of NFkB ligand (RANKL). Flow cytometry was utilized to analyze osteoclast precursors (OCPs) and T cell phenotype. Tumour necrosis factor a (TNF-a), RANKL and osteoprotegerin (OPG) were quantified in cell culture supernatants by ELISA. The effects of RANKFc and anti-TNF-a antibodies were also investigated to determine their ability to inhibit osteoclastogenesis. In addition, bone conditions and phenylalanine levels in PKU patients were clinically evaluated. Principal Findings: Several in vitro studies in PKU patients’ cells identified a potential mechanism of bone formation inhibition commonly associated with this disorder. First, PKU patients disclosed an increased osteo