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.