title: Fam3c modulates osteogenic cell differentiation and affects bone volume and cortical bone mineral density.
abstract: Fam3c, a cytokine-like growth factor, has been suggested to have a role in epithelial-to-mesenchymal transition (EMT), tumor growth and metastasis. A single-nucleotide polymorphism affecting bone mineral density has been found in the first intron of the Fam3c gene in a study analyzing an Asian population cohort. Other independent studies on different population cohorts have found the fam3c locus to be associated with bone mineral density and fractures. In order to investigate the role of Fam3c in bone biology, we have generated a Fam3c knock-out (KO) mouse strain. The Fam3c KO mice were found to have normal appearance, behavior and fertility, but small changes in bone morphology and content were also observed. Micro-CT analysis of tibiae of the female mice revealed decreased number of trabeculae. In male mice the changes in the bone phenotype were smaller, but hematological changes were observed. Furthermore, there was a negative correlation between body weight and tibial trabecular and cortical bone volume in the male KO mice. There was a small increase in cortical bone mineral density, but in the lateral direction of tibiae the breaking strength was reduced. Fam3c KO bone marrow cells showed accelerated osteogenic differentiation and mineralization in vitro. The reduced number of bone trabeculae in Fam3c KO mice and the stimulated osteogenic differentiation indicate a role for Fam3c in osteoblast differentiation and bone homeostasis.
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland; School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Turku Center of Disease Modeling, University of Turku, Turku, Finland.
authors.forename: Jorma A
authors.initials: JA
authors.lastname: Määttä
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Ameya
authors.initials: A
authors.lastname: Bendre
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Laanti
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Kalman G
authors.initials: KG
authors.lastname: Büki
authors.affiliation: Turku Center of Disease Modeling, University of Turku, Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Rantakari
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Tervola
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Saarimäki
authors.affiliation: Turku Center of Disease Modeling, University of Turku, Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Härkönen
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Kalervo
authors.initials: K
authors.lastname: Väänänen