Lack of a direct effect of estrogen on proliferation and differentiation of normal human osteoblast‐like cells

Although osteoblasts contain estrogen receptors, it is unclear whether estrogen has direct effects on osteoblast proliferation and differentiation. We evaluated the effects of 17β‐estradiol treatment (1 pM to 10 nM) on the proliferation and differentiation of cultured normal adult human cells that expressed many of the phenotypic characteristics and hormonal sensitivities of mature osteoblasts (hOB cells). Treatment of hOB cells with estradiol for as long as 144 h did not affect the rate of DNA synthesis and had minimal, if any, effects on differentiated function. Whereas alkaline phosphatase activity was increased by nearly twofold (P < 0.01) when the hOB cells were treated with 1 nM 1,25‐dihydroxyvitamin D₃ [1,25‐(OH)₂D₃], treatment with estradiol had no effect when given alone and did not affect the cells' response to 1,25‐(OH)₂D₃. Similarly, the release of bone gla protein (BGP, osteocalcin) was induced by treatment with 1,25‐(OH)₂D₃ (P < 0.05), but estradiol treatment did not affect this response. Cellular levels of mRNA for alkaline phosphatase and BGP were not altered by estradiol treatment. We conclude that estradiol treatment does not have major effects on the growth or differentiation of cultured hOB cells. These results are consistent with previous observations in vivo that indicate estrogen acts principally to decrease bone resorption, not to modulate its formation.