A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro

Verhaar, H.J.J.; Damen, Cora A.; Duursma, S. A.; Scheven, Ben A.

doi:10.1016/8756-3282(94)90293-3

Cited by 53 publications

(32 citation statements)

References 33 publications

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“…(22,23) P also increases proliferation and differentiation of normal osteoblasts. (24,25) Some studies show that E 2 tends to be more of a differentiation-inducer, whereas P enhances osteoblast growth. (25,26) P appears also to inhibit bone resorption by mature osteoclasts isolated from rat long bones in a dose dependent manner (27) and pharmacological doses of progestagens decrease the urinary output of calcium and Hyp in humans.…”

Section: Discussionmentioning

confidence: 99%

“…(24,25) Some studies show that E 2 tends to be more of a differentiation-inducer, whereas P enhances osteoblast growth. (25,26) P appears also to inhibit bone resorption by mature osteoclasts isolated from rat long bones in a dose dependent manner (27) and pharmacological doses of progestagens decrease the urinary output of calcium and Hyp in humans. (28) Cyclic medroxyprogesterone increases spine BMD in women with abnormal menstrual cycles (29) and estrogen/progesterone replace- …”

Section: Discussionmentioning

confidence: 99%

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Changes in Bone Resorption During the Menstrual Cycle

Chiu

Mayes³

et al. 1999

Journal of Bone and Mineral Research

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To determine if the cyclic changes of female sex hormones during the menstrual cycle are related to changes in bone formation and resorption, we measured serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC) and bone resorption markers, serum and urine deoxypyridinoline (Dpyr), three times per week during one menstrual cycle in 20 healthy premenopausal women. Serum estradiol (E 2 ) and progesterone (P) showed characteristic cyclic fluctuations. Serum Dpyr was higher during the follicular phase (

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Changes in Bone Resorption During the Menstrual Cycle

Chiu

Mayes³

et al. 1999

Journal of Bone and Mineral Research

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“…Compared to cell lines like MCF-7 human breast cancer cells [Kasid et al, 1984], these osteoblast models contain low numbers (60-4,500/ cell) of high affinity (K d 5 0.05-1.1 nM) ERs [Komm et al, 1988;Eriksen et al, 1988;Kaplan et al, 1988;Etienne et al, 1990;Benz et al, 1991;Keeting et al, 1992;Masuyama et al, 1992;Migliaccio et al, 1992;Davis et al, 1994]. Estrogen has been reported to have numerous effects on osteoblasts in vitro: these include the regulation of DNA synthesis and cellular proliferation [Gray et al, 1987;Bankson et al, 1989;Ernst et al, 1989;Liel et al, 1992;Masuyama et al, 1992;Ikegami et al, 1994;Majeska et al, 1994;Verhaar et al, 1994]; the stimulation of alkaline phosphatase, creatine kinase, lactate dehydrogenase, g-glutamyl transferase, and aspartate aminotransferase activity [Gray et al, 1987;Bankson et al, 1989;Somjen et al, 1989;Majeska et al, 1994;Verhaar et al, 1994]; the upregulation of transferrin, transforming growth factor (TGF)-b1, insulin-like growth factor (IGF)-I, a1 type (I) procollagen, progesterone receptor, c-fos, heat-shock protein, and interleukin-1b (IL-1b) expression [Komm et al, 1988;Eriksen et al, 1988;Bankson et al, 1989;Gray et al, 1989a,b;Oursler et al, 1991;Cooper and Uoshima, 1994;Harris et al, 1992;Majeska et al, 1994;Pivirotto et al, 1995]; the suppression of cytokineinduced IL-6 and tumor necrosis factor-a (TNF-a) expression [Girasole et al, 1992;…”

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confidence: 98%

Functional properties of a conditionally phenotypic, estrogen-responsive, human osteoblast cell line

Bodine¹,

Green

Harris³

et al. 1997

J. Cell. Biochem.

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Osteoblasts are established targets of estrogen action in bone. We screened 66 conditionally immortalized clonal human osteoblast cell lines for estrogen receptors (ERs) using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for ER alpha mRNA and transactivation of adenovirus-estrogen response element (ERE)-tk-luciferase by 17 beta-estradiol (17 beta-E2) for functional ER protein. One of these cell lines, termed HOB-03-CE6, was chosen for further characterization. The cells, which were conditionally immortalized with a temperature-sensitive SV40 large T antigen, proliferated at the permissive temperature (34 degrees C) but stopped dividing at the nonpermissive temperature (> or = 39 degrees C). Alkaline phosphatase activity and osteocalcin secretion were upregulated by 1 alpha, 25-dihydroxyvitamin D3 in a dose-dependent manner. The cells also expressed type I collagen and other bone matrix proteins, secreted a variety of growth factors and cytokines, formed mineralized nodules based on alizarin red-S and von Kossa histochemical staining, and responded to dexamethasone, all-trans retinoic acid, and transforming growth factor-beta 1. This cell line expressed 42-fold less ER message than MCF-7 human breast cancer cells, as determined by quantitative RT-PCR. However, adenovirus-ERE-tk-luciferase activity was upregulated three- to fivefold in these cells by 17 beta-E2 with an EC50 of 64 pM. Furthermore, this upregulation was suppressed by co-treatment with the anti-estrogen ICI-182, 780. Cytosolic extracts of these cells specifically bound [125I]-17 beta-E2 in a concentration-dependent manner with a Bmax of 2.7 fmoles/mg protein (approximately 1,200 ERs/cell) and a Kd of 0.2 nM. DNA gel-shift analysis using a [32P]-ERE demonstrated the presence of ERs in nuclear extracts of these cells. Moreover, binding of the extracts to this ERE was blocked by a monoclonal antibody to the human ER DNA-binding domain. We evaluated these cells for 14 of 20 reported endogenous responses to 17 beta-E2 in osteoblasts. Although most of these responses appeared to be unaffected by the steroid, 17 beta-E2 suppressed parathyroid hormone-induced cAMP production, as well as basal interleukin-6 mRNA expression; conversely, the steroid upregulated the steady-state expression of alkaline phosphatase message in these cells. In summary, we have identified a clonal, conditionally phenotypic, human osteoblast cell line that expresses functional ERs and exhibits endogenous responses to 17 beta-E2. This cell line will be a valuable in vitro model for exploring some of the molecular mechanisms of estrogen action in bone.

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“…On the other hand, low levels of E 2 are associated with osteoporosis in postmenopausal women. E 2 induces the proliferation and differentiation of primary osteoblasts derived from mice, rats, and humans (Ernest et al 1988, Scheven et al 1992, Verhaar et al 1994, Qu et al 1998, O'Shaughnessy et al 2000, Chen et al 2002. Further, E 2 increases Igf1 expression in osteoblasts, and IGF1 secreted from osteoblasts stimulates osteoblast proliferation (Ernst et al 1989, Kassem et al 1998.…”

Section: Discussionmentioning

confidence: 99%

Autocrine effects of neuromedin B stimulate the proliferation of rat primary osteoblasts

Saito

Nakamachi²,

Inoue³

et al. 2013

Journal of Endocrinology

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Neuromedin B (NMB) is a mammalian bombesin-like peptide that regulates exocrine/ endocrine secretion, smooth muscle contraction, body temperature, and the proliferation of some cell types. Here, we show that mRNA encoding Nmb and its receptor (Nmbr) are expressed in rat bone tissue. Immunohistochemical analysis demonstrated that NMB and NMBR colocalize in osteoblasts, epiphyseal chondrocytes, and proliferative chondrocytes of growth plates from mouse hind limbs. Then, we investigated the effect of NMB on the proliferation of rat primary cultured osteoblasts. Proliferation assays and 5-bromo-2 0 -deoxyuridine incorporation assays demonstrated that NMB augments the cell number and enhances DNA synthesis in osteoblasts. Pretreatment with the NMBR antagonist BIM23127 inhibited NMB-induced cell proliferation and DNA synthesis. Western blot analysis showed that NMB activates ERK1/2 MAPK signaling in osteoblasts. Pretreatment with the MAPK/ERK kinase inhibitor U0126 attenuated NMB-induced cell proliferation and DNA synthesis. We also investigated the effects of molecules that contribute to osteoblast proliferation and differentiation on Nmb expression in osteoblasts. Real-time PCR analysis demonstrated that 17b-estradiol (E 2 ) and transforming growth factor b1 increase and decrease Nmb mRNA expression levels respectively. Finally, proliferation assays revealed that the NMBR antagonist BIM23127 suppresses E 2 -induced osteoblast proliferation. These results suggest that NMB/NMBR signaling plays an autocrine or paracrine role in osteoblast proliferation and contributes to the regulation of bone formation.

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A comparison of the action of progestins and estrogen on the growth and differentiation of normal adult human osteoblast-like cells in vitro

Cited by 53 publications

References 33 publications

Changes in Bone Resorption During the Menstrual Cycle

Changes in Bone Resorption During the Menstrual Cycle

Functional properties of a conditionally phenotypic, estrogen-responsive, human osteoblast cell line

Autocrine effects of neuromedin B stimulate the proliferation of rat primary osteoblasts

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