Nonhypercalcemic Analogs of Vitamin D Stimulate Creatine Kinase B Activity in Osteoblast-Like ROS 17/2.8 Cells and Up-regulate Their Responsiveness to Estrogens

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

“…However, in both mature and older males, JKF increased basal CK specific activity. Pretreatment with any of the analogs upregulated the responses to estrogen in our human osteoblast cell system as it had in ROS 17/2.8 cells [18,23] or in prepubertal rat diaphyseal bone [6,7]. The up regulation of androgen action (Fig.…”

“…Therefore, to avoid toxic effects, we tested structurally modified "non-hypercalcemic" analogues for their potency in upregulating estrogen activity. We reported that multiple treatments with "non-hypercalcemic" analogs of Vitamin D, such as MC 1288, CB 1093, EB 1089 and the demonstrably non-calcemic JKF 1624 F2-2 [22] stimulated the specific activity of CK in ROS 17/2.8 osteoblast-like cells [18,23]. Moreover, pretreatment of skeletal-derived cells with these analogs upregulated both responsiveness and sensitivity to E 2 [23] and SERMS [6].…”

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].…”

Modulation of the response to estradiol-17β of rat vascular tissues by a non calcemic vitamin D analog

“…The specific activity of creatine kinase (CK) is known to be induced by estrogens in vivo and in vitro [10,11], and, therefore, can be used as an estrogen receptor (ER) response marker. In previous reports, we showed that the non hypercalcemic analog of vitamin D, JK 1624 F2-2 (JKF) [12] increased the effects of E 2 in terms of both the absolute response and sensitivity to E 2 in skeletal cells and skeletal tissues [13] and in vascular cells in culture [14].…”