title: Gene expression profile analysis of human mesenchymal stem cells from herniated and degenerated intervertebral discs reveals different expression of osteopontin.
abstract: Gene expression analysis provides an effective methodology to identify clinically relevant genes implicated in intervertebral disc (IVD) pathology. The analysis of gene profile in mesenchymal stem cells (MSCs) from human herniated IVD (H-IVD) and degenerated IVD (D-IVD) has not yet been investigated. We present in this study a characterization of MSCs isolated from clinically categorized H-IVD and D-IVD disc samples. H-IVD-MSCs and D-IVD-MSCs showed multipotent mesenchymal differentiation ability, expressing positivity for adipogenic, osteogenic, and chondrogenic markers with an immunophenotypical profile representative of MSCs. FACS analyses revealed a higher expression of CD44 in D-IVD-MSCs compared to H-IVD-MSCs. Gene expression profile revealed that most genes under investigation displayed large variations and were not significantly different in the two types of analyzed IVD-MSCs. Conversely, the gene expression of osteopontin (OPN), a protein involved in bone matrix mineralization and extracellular matrix destruction, was found markedly increased (more than 400-fold) in D-IVD-MSCs compared to H-IVD-MSCs. Moreover, the OPN protein expression was detectable only in D-IVD-MSCs, and its levels were directly related with D-IVD severity. These findings suggest that an abnormal expression of OPN in D-IVD-MSCs occurs and plays a pivotal role in the pathophysiological process of human disc degeneration. We speculate that the regulation of the OPN pathway might be a therapeutic target to counteract disc degeneration.
authors.affiliation: 1 Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, University of Milan , Milan, Italy .
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marfia
authors.forename: Stefania Elena
authors.initials: SE
authors.lastname: Navone
authors.forename: Clara
authors.initials: C
authors.lastname: Di Vito
authors.forename: Silvia
authors.initials: S
authors.lastname: Tabano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Giammattei
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Cristofori
authors.forename: Roberta
authors.initials: R
authors.lastname: Gualtierotti
authors.forename: Carlo
authors.initials: C
authors.lastname: Tremolada
authors.forename: Mario
authors.initials: M
authors.lastname: Zavanone
authors.forename: Manuela
authors.initials: M
authors.lastname: Caroli
authors.forename: Francesco
authors.initials: F
authors.lastname: Torchia
authors.forename: Monica
authors.initials: M
authors.lastname: Miozzo
authors.forename: Paolo
authors.initials: P
authors.lastname: Rampini
authors.forename: Laura
authors.initials: L
authors.lastname: Riboni
authors.forename: Rolando
authors.initials: R
authors.lastname: Campanella
mesh_terms: D000328:Adult; D000368:Aged; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002455:Cell Division; D002469:Cell Separation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D007405:Intervertebral Disc Displacement / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000166:cytology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D053495:Osteopontin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D053495:Osteopontin