title: Uremic Serum Impairs Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stromal Cells.
abstract: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is characterized by an increased fracture risk. Bone marrow mesenchymal stromal cells (BMSCs) may be involved in the pathogenesis of bone disease and, in view of their promising potential applications in bone tissue engineering, the effect of uremia on BMSCs regenerative potential represents a central issue. The present study evaluated in vitro the effect of a serum pool from hemodialysis patients on BMSCs to observe its influence on osteogenic differentiation. Besides alterations in spatial organization and cytotoxicity along with hyperproliferation, gene expression analysis suggested an impairment in the osteogenic differentiation. More importantly, Receptor activator of nuclear factor kappa-B ligand (RANKL) was upregulated with a mild reduction in osteoprotegerin levels. In summary, uremic environment seems to impair BMSCs osteogenic differentiation. Moreover BMSCs themselves may enhance osteoclastogenesis, feasibly contributing to the altered bone remodeling in CKD-MBD patients. J. Cell. Physiol. 232: 2201-2209, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy.|Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Della Bella
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Department Rizzoli RIT, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pagani
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Department Rizzoli RIT, Bologna, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giavaresi
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola Hospital, University of Bologna, Bologna, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Capelli
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola Hospital, University of Bologna, Bologna, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Comai
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola Hospital, University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Donadei
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola Hospital, University of Bologna, Bologna, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cappuccilli
authors.affiliation: Nephrology Dialysis and Transplantation Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola Hospital, University of Bologna, Bologna, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: La Manna
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy.|Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Department Rizzoli RIT, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010012:Osteogenesis; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D006435:Renal Dialysis; D013997:Time Factors; D014511:Uremia / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000469:Alkaline Phosphatase