title: Human myeloma cell lines induce osteoblast downregulation of CD99 which is involved in osteoblast formation and activity.
abstract: CD99 is a transmembrane glycoprotein expressed in physiological conditions by cells of different tissues, including osteoblasts (OBs). High or low CD99 levels have been detected in various pathological conditions, and the supernatant of some carcinoma cell lines can modulate CD99 expression in OB-like cells. In the present work we demonstrate for the first time that two different human myeloma cell lines (H929 and U266) and, in a less degree, their conditioned media significantly downregulate CD99 expression in normal human OBs during the differentiation process. In the same experimental conditions the OBs display a less differentiated phenotype as demonstrated by the decreased expression of RUNX2 and Collagen I. On the contrary, when CD99 was activated by using a specific agonist antibody, the OBs become more active as demonstrated by the upregulation of Alkaline Phosphatase, Collagen I, RUNX2, and JUND expression. Furthermore, we demonstrate that the activation of CD99 is able to induce the phosphorylation of ERK 1/2 and AKT intracellular signal transduction molecules in the OBs.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Oranger
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Giacomina
authors.identifier: 0000-0002-0681-1432
authors.initials: G
authors.lastname: Brunetti
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carbone
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Graziana
authors.identifier: 0000-0001-8501-5399
authors.initials: G
authors.lastname: Colaianni
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mongelli
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Gigante
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Tamma
authors.affiliation: Department of Clinical and Experimental Medicine, Medical School, University of Foggia, Viale Luigi Pinto 1, 71100 Foggia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mori
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Benedetto
authors.affiliation: CRS Development of Biomolecular Therapies, Laboratory of Experimental Oncology, Orthopaedic Institute of Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Marika
authors.identifier: 0000-0001-7147-6960
authors.initials: M
authors.lastname: Sciandra
authors.affiliation: CRS Development of Biomolecular Therapies, Laboratory of Experimental Oncology, Orthopaedic Institute of Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Selena
authors.identifier: 0000-0002-6034-517X
authors.initials: S
authors.lastname: Ventura
authors.affiliation: CRS Development of Biomolecular Therapies, Laboratory of Experimental Oncology, Orthopaedic Institute of Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
mesh_terms: D000071443:12E7 Antigen; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D017077:Culture Media, Conditioned; C559371:JunD protein, human; D016755:Proto-Oncogene Proteins c-jun; C493709:RUNX2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase