Määttä Jorma A, Bendre Ameya, Laanti Mervi, Büki Kalman G, Rantakari Pia, Tervola Päivi, Saarimäki Johanna, Poutanen Matti, Härkönen Pirkko, Väänänen Kalervo
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.
Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
Bonekey Rep. 2016 Apr 6;5:787. doi: 10.1038/bonekey.2016.14. eCollection 2016.
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.
Fam3c是一种细胞因子样生长因子，已被认为在上皮-间质转化（EMT）、肿瘤生长和转移中发挥作用。在一项对亚洲人群队列的研究分析中，在Fam3c基因的第一个内含子中发现了一个影响骨矿物质密度的单核苷酸多态性。对不同人群队列的其他独立研究发现，Fam3c基因座与骨矿物质密度和骨折有关。为了研究Fam3c在骨生物学中的作用，我们构建了一种Fam3c基因敲除（KO）小鼠品系。发现Fam3c基因敲除小鼠外观、行为和生育能力正常，但也观察到骨形态和骨含量有微小变化。对雌性小鼠胫骨的显微CT分析显示小梁数量减少。在雄性小鼠中，骨表型的变化较小，但观察到血液学变化。此外，雄性基因敲除小鼠的体重与胫骨小梁和皮质骨体积之间存在负相关。皮质骨矿物质密度有小幅增加，但在胫骨外侧方向，断裂强度降低。Fam3c基因敲除的骨髓细胞在体外显示出加速的成骨分化和矿化。Fam3c基因敲除小鼠骨小梁数量减少以及成骨分化受到刺激，表明Fam3c在成骨细胞分化和骨稳态中发挥作用。
