Abstract
Sex and genetic factors determine skeletal mass, and we tested whether bone histomorphometric parameters were sexually dimorphic in femurs from 1 to 6 month old C57BL/6 mice. Trabecular bone volume declined more rapidly in female mice than in male littermates because of enhanced bone resorption. Although bone formation was not different between sexes, female mice exhibited a higher number of osteoblasts than male littermates, suggesting that osteoblasts from female mice may have a reduced ability to form bone. To determine the impact of sex on osteoblastogenesis, we investigated the potential for osteoblastic differentiation of bone marrow stromal cells from C57BL/6, Friend leukemia virus-B (FVB), C3H/HeJ and BALB/c mice of both sexes. Bone marrow stromal cells from female FVB, C57BL/6 and C3H/HeJ mice exhibited lower Alpl and Osteocalcin expression and alkaline phosphatase activity, and formed fewer mineralized nodules than cells from male littermates. Proliferative capacity was greater in cells from male than female C57BL/6, but not FVB, mice. Sorting of bone marrow stromal cells from mice expressing an α-Smooth muscle actin-green fluorescent protein transgene, revealed a higher yield of mesenchymal stem cells in cultures from male mice than in those from female littermates. Sex had a modest impact on osteoblastic differentiation of mesenchymal stem cells. To determine the influence of sex and genetic factors on osteoblast function, calvarial osteoblasts were harvested from C57BL/6, FVB, C3H/HeJ and BALB/c mice. Alpl expression and activity were lower in osteoblasts from C57BL/6 and C3H/HeJ, but not FVB or BALB/c, female mice than in cells from littermates. Sex had no effect on osteoclastogenesis of bone marrow cultures of C57BL/6 mice, but osteoblasts from female mice exhibited higher Rankl and lower Opg expression than cells from male littermates. In conclusion, osteoblastogenesis is sexually dimorphic and influenced by genetic factors.
Highlights
Human and rodent males attain higher peak bone mass during growth than females [1]
To investigate whether sex and genetic factors have an impact on osteoblast differentiation and function, we studied the potential for osteoblastogenesis of bone marrow stromal cells and the function of calvarial osteoblasts from male or female C57BL/6, tropism for Friend leukemia virus-B (FVB), BALB/c or C3H/HeJ mice
We confirmed that cancellous bone volume declines in maturing female C57BL/6 mice, whereas it remains stable in male littermates
Summary
Human and rodent males attain higher peak bone mass during growth than females [1]. Trabecular bone declines more rapidly and at a younger age in maturing female than in male C57BL/6 mice, so that adult female mice have less cancellous bone than male mice [2]. Sex hormones regulate bone remodeling, but skeletal differences related to gender become evident prior to the onset of sexual maturity [3,4]. Genetic determinants regulate bone mass acquisition, and differences in androgen and estrogen levels do not seem to account for skeletal sexual dimorphism [5,6]. The balance of osteoblast and osteoclast activity maintains skeletal remodeling and integrity, and alterations in osteoclast or osteoblast number or function can lead to changes in bone mass [7]. Osteoblast number is determined by the replication and differentiation of bone marrow mesenchymal stem cells toward osteoblasts, the death of mature cells and their differentiation into lining cells or osteocytes [8,9]. Rankl activity is inhibited by the soluble Rankl receptor osteoprotegerin (Opg), so that the Rankl to Opg ratio determines the number and activity of osteoclasts [13,14]
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