title: Hurler disease bone marrow stromal cells exhibit altered ability to support osteoclast formation.
abstract: Mucopolysaccharidosis type I (MPS IH; Hurler syndrome) is a rare genetic disorder that is caused by mutations in the α-L-iduronidase (IDUA) gene, resulting in the deficiency of IDUA enzyme activity and intra-cellular accumulation of glycosaminoglycans. A characteristic skeletal phenotype is one of the many clinical manifestations in Hurler disease. Since the mechanism(s) underlying these skeletal defects are not completely understood, and bone and cartilage are mesenchymal lineages, we focused on the characterization of mesenchymal cells isolated from the bone marrow (BM) of 5 Hurler patients. IDUA-mutated BM stromal cells (BMSC) derived from MPS IH patients exhibited decreased IDUA activity, consistent with the disease genotype. The expansion rate, phenotype, telomerase activity, and differentiation capacity toward adipocytes, osteoblasts, chondrocytes, and smooth muscle cells in vitro of the MPS I BMSC lines were similar to those of BMSC from age-matched normal control donors. MPS I BMSC also had a similar in vivo osteogenic capacity as normal BMSC. However, MPS I BMSC displayed an increased capacity to support osteoclastogenesis, which may correlate with the up-regulation of the RANKL/RANK/OPG molecular pathway in MPS I BMSC compared with normal BMSC.
authors.affiliation: Pediatric Department, Dulbecco Telethon Institute at Tettamanti Research Center, University of Milano-Bicocca, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gatto
authors.forename: Daniela
authors.initials: D
authors.lastname: Redaelli
authors.forename: Agnese
authors.initials: A
authors.lastname: Salvadè
authors.forename: Simona
authors.initials: S
authors.lastname: Marzorati
authors.forename: Benedetto
authors.initials: B
authors.lastname: Sacchetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Ferina
authors.forename: Valerie D
authors.initials: VD
authors.lastname: Roobrouck
authors.forename: Francesca
authors.initials: F
authors.lastname: Bertola
authors.forename: Michela
authors.initials: M
authors.lastname: Romano
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Villani
authors.forename: Laura
authors.initials: L
authors.lastname: Antolini
authors.forename: Attilio
authors.initials: A
authors.lastname: Rovelli
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Mara
authors.initials: M
authors.lastname: Riminucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianco
authors.forename: Marta
authors.initials: M
authors.lastname: Serafini
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D002648:Child; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000235:genetics / Q000378:metabolism; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505688:TNFSF11 protein, human; D007068:Iduronidase