It is well known that sex differences exist concerning the severity of osteoporosis and bone metabolism, suggesting that factors other than sex hormones might be responsible for sex differences of bone metabolism. We therefore examined sex differences of osteoblast phenotypes of mouse osteoblasts and then performed comparative gene expression analyses using a comprehensive DNA microarray between female and male osteoblasts. Alkaline phosphatase (ALP) activity, mineralization, and the expression of Osterix, ALP, and bone sialoprotein were significantly lower in mouse female osteoblasts compared with male osteoblasts. We identified Serpina3n, a novel serine protease inhibitor, as the gene whose expression has the highest ratio of females to males. A reduction in endogenous levels of Serpina3n by small interfering RNA significantly enhanced the mRNA levels of Runx2, ALP, osteocalcin, and type I collagen (Col1a1) in both male and female osteoblasts. Moreover, Serpina3n overexpression significantly suppressed the mRNA levels of Osterix, ALP, osteocalcin, and Col1a1 in MC3T3-E1 cells. Serpina3n overexpression did not affect Osterix, ALP, and osteocalcin mRNA levels enhanced by bone morphogenetic protein (BMP)-2 in ST2 cells, adipogenic differentiation in ST2 and 3T3-L1 cells, and receptor activator of nuclear factor κB ligand-induced osteoclast formation in RAW264.7 cells, although it significantly suppressed mineralization in ST2 cells differentiated into osteoblasts by BMP-2. In conclusion, we found Serpina3n as the most female osteoblast-dominant gene. Serpina3n exerts a suppression of the osteoblast phenotypes such as Col1a1 expression and ALP activity in differentiated osteoblasts, which might partly explain sex differences of the osteoblast phenotypes in mice.
Pubmed ID: 30304388 RIS Download
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This unknown targets SERPINA3N
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Goat IgG
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsCell line ST2 is a Stromal cell line with a species of origin Mus musculus
View all literature mentionsCell line 3T3-L1 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line ATDC-5 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Goat IgG
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis unknown targets SERPINA3N
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsCell line 3T3-L1 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line ATDC-5 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line ST2 is a Stromal cell line with a species of origin Mus musculus
View all literature mentions