Treatment with non-hypercalcemic analogs of 1,25-dihydroxyvitamin D3 increases responsiveness to 17β-estradiol, dihydrotestosterone or raloxifene in primary human osteoblasts

Modulation of response to estrogens in cultured human female bone cells by a non-calcemic Vitamin D analog: changes in nuclear and membranal binding

“…The increased responsiveness to estrogens after pretreatment with Vitamin D, previously demonstrated in skeletal-derived cells in vitro [9] was demonstrated as well in primary human bone cells, apparently due to modulation of ERs [8]. All forms of ERs were modulated significantly by JKF treatment except the 67k ER␣ in post-menopausal women.…”

“…In post-menopausal bone cells, the increase of 32k ER␣ was 2.7-fold, with no change in 67k ER␣. Both 37 and 63k ER␤ forms, were increased by 11-and 4-fold, respectively [8].…”

“…This marker can be used to measure the response to of E 2 in cells containing low concentrations of E 2 receptors (ERs) [5,6]. We found that pretreatment with the demonstrably non hypercalcemic Vitamin D analog JKF 1624 F2-2 (JKF) [7] upregulated responsiveness and sensitivity to E 2 in human bone derived cell cultures as measured by the stimulation of CK [8]. This increase was accompanied by an increase in estrogen receptors [9].…”

Less calcemic Vitamin D analogs enhance creatine kinase specific activity and modulate responsiveness to gonadal steroids in the vasculature

“…This finding also complements our previous findings in human vascular smooth muscle cells in vitro, in which pretreatment with the Vitamin D JKF increased both ER␣ mRNA and protein expression [8]. These results also resemble observations in cultured human bone cells, in which pretreatment with JKF or CB significantly up regulated the response to E 2 in all female-derived cells and to DHT in mature male-derived cells [22][23]. Vitamin D was also reported to induce ER␣ expression in two prostate cancer cell lines [24].…”

Responsiveness to phytoestrogens in primary human osteoblasts is modulated differentially by a “less-calcemic” analog of 1,25 dihydroxyvitamin D3: JK 1624F2-2 (JKF)

“…However, the use of Vitamin D, is restricted by its hypercalcemic effects [25]. We reported that multiple treatments with "less-calcemic" analogs of Vitamin D, particularly JKF 1624 F2-2 [26] stimulated the specific activity of CK in ROS 17/2.8 osteoblast-like cells [27,28]. Pre-treatment of skeletal-derived cells with these analogs, upregulated both responsiveness and sensitivity to E 2 [27].…”