title: Lim mineralization protein is involved in the premature calvarial ossification in sporadic craniosynostoses.
abstract: Sporadic mono-sutural craniosynostosis represents a highly prevalent regional bone disorder, where a single cranial suture undergoes premature ossification due to a generally unclear etiopathogenesis. The LIM mineralization protein (LMP) was recently described as an efficient osteogenic molecule involved in osteoblast differentiation, expressed in calvarial tissues upon corticosteroid-osteogenic induction and used as a potent inducer of bone formation in several animal models. In this study, calvarial cells isolated from both prematurely fused and physiologically patent sutures of children with sporadic craniosynostosis, were used as an in vitro paradigmatic model for the study of the molecular events involved in calvarial osteogenesis, focusing on the possible role of the LMP-related osteogenic signaling. Calvarial cells isolated from both patent and fused sutures expressed a mesenchymal-like immunophenotype. Cells isolated from fused sutures displayed an increased osteogenic potential, being able to undergo spontaneous mineralization and premature response to osteogenic induction, leading to in vitro bone nodule formation. The expression of LMP and its target genes (bone morphogenetic protein-2, osteocalcin and Runt-related transcription factor 2) was significantly up-regulated in cells derived from the fused sutures. Upon silencing the expression of LMP in fused suture-derived cells, the osteogenic potential along with the expression of osteo-specific transcription factors decreased, restoring the "physiologic" cell behavior. These results suggested that: 1. mesenchymal cells residing in fused sutures display a constitutionally active osteogenic disposition leading to the premature suture ossification; 2. the molecular basis of the overactive osteogenic process may at least in part involve a deregulation of the LMP-related pathway in calvarial cells.
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica S. Cuore, Rome, Italy. wanda.lattanzi@rm.unicatt.it
authors.forename: Wanda
authors.initials: W
authors.lastname: Lattanzi
authors.forename: Marta
authors.initials: M
authors.lastname: Barba
authors.forename: Federica
authors.initials: F
authors.lastname: Novegno
authors.forename: Luca
authors.initials: L
authors.lastname: Massimi
authors.forename: Valentina
authors.initials: V
authors.lastname: Tesori
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Tamburrini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galgano
authors.forename: Camilla
authors.initials: C
authors.lastname: Bernardini
authors.forename: Massimo
authors.initials: M
authors.lastname: Caldarelli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Michetti
authors.forename: Concezio
authors.initials: C
authors.lastname: Di Rocco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D001483:Base Sequence; D002675:Child, Preschool; D003398:Craniosynostoses / Q000503:physiopathology*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D017931:DNA Primers; D006801:Humans; D007223:Infant; D060588:LIM Domain Proteins / Q000502:physiology*; D009999:Ossification, Heterotopic / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D012886:Skull / Q000503:physiopathology*; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human; D051785:Smad Proteins