Cytology and autoradiography of estrogen-induced differentiation of avian endosteal cells

Kusuhara, Seiji; Schraer, Harald

doi:10.1007/bf02411267

Cited by 41 publications

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“…Kinetic study would be needed to rule out this possibility. Our findings, nevertheless, are consistent with: 1) the demonstration of the uptake of radiolabeled estrogen in the bone marrow along the endosteum in mice (Budy, 1962) and of the induction of endosteal cell differentiation with a subsequent increase in osteoblast formation in quail (Kusuhara and Schraer, 1982;Bowman and Miller, 19861, suggesting the site of hormone action; 2) a short-term autoradiographic study showing a n increased number of metaphyseal osteoblasts labeled with 3H-thymidine in mice 24 hours after estrogen treatment (Simmons, 1963); 3) observations of increased 3H-thymidine incorporation or cell proliferation in cultures of osteoblastic cells (Vaishnav et al, 1984;Ernst et al, 1988Ernst et al, , 1989 and increased proliferation of osteogenic cells in cultures of fetal long bones (Liskova-Kiar, 1978) after estrogen treatment; and 4) a recent report of direct stimulation of bone formation in ovariectomized rats given estrogen locally (Takano-Yamamoto and Rodan, 1990). It has been suggested, based on gross histological observations, that the increase in bone mass seen in tibia andlor femoral shafts of estrogen-treated mice is due to the extension of unresorbed metaphyseal trabecular bone into the diaphysis Silberberg, 1941a, b, 1971;Urist et al, 1950).…”

Section: Discussionsupporting

confidence: 92%

Bone‐cell changes in estrogen‐induced bone‐mass increase in mice: Dissociation of osteoclasts from bone surfaces

Liu

Howard

1991

Anat. Rec.

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Early studies in certain avian and mammalian species have described estrogen-associated bone-cell changes, which were based on bone cells that were neither quantified nor identified histochemically (osteoclasts). In the experiments described here, weanling female mice were given a pharmacological dose of 17 beta-estradiol benzoate (1 mg/week) for 1 and 4 weeks, and changes in osteoclasts and osteoblasts were assessed in tibial metaphyses and diaphyses. In the proximal metaphysis, the number of osteoclasts/mm surface length was significantly reduced by estrogen at 1 week (43%) and 4 weeks (64%), which was accompanied by significant increases in the number of osteoclasts in the marrow space not in contact with bone surfaces (no./mm2: 382% and 999%, respectively). These increases, along with observations of decreased osteoclast size (19%), of changes in osteoclast morphology, and of numerous acid-phosphatase-positive fragments in the marrow space, suggest that estrogen treatment causes the dissociation and disintegration, and thus decreased activity, of osteoclasts. The above changes were accompanied by more than 48% increases in the number of trabecular osteoblasts. In the diaphysis, the number of endosteal osteoclasts was significantly decreased by estrogen at 1 week (32%), but was not significantly changed at 4 weeks. These changes were attended by significant increases in the number of osteoclasts in the marrow space not in contact with bone surfaces (no./mm2: 393% at 1 week and 342% at 4 weeks). The number of endosteal osteoblasts was also increased by estrogen at 1 week (132%), and so was the size of endosteal osteoblasts (39% at 1 week and 81% at 4 weeks). Comparable results were obtained when a lower dose of 17 beta-estradiol benzoate (20 micrograms/week) was given to ovariectomized mice. The increase in bone mass and its associated cell changes following estrogen treatment were also found in athymic nude mice, suggesting that these bone/bone cell changes are independent of the thymus.

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Section: Discussionsupporting

confidence: 92%

Bone‐cell changes in estrogen‐induced bone‐mass increase in mice: Dissociation of osteoclasts from bone surfaces

Liu

Howard

1991

Anat. Rec.

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“…A major unanswered question is whether estrogen action on bone in vivo is direct or indirect (4,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). It has been suggested that in vivo estrogen promotes the systemic production of growth factors, so-called estromedins, or the removal of growth inhibitors, estrocolyons, elsewhere in the body (42).…”

Section: Discussionmentioning

confidence: 99%

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

Takano‐Yamamoto

Rodan

1990

Proc. Natl. Acad. Sci. U.S.A.

163

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High-affinity nuclear binding sites for 17 (3-estradiol (17(3E2) were recently found in bone cells; however, the mechanism by which estrogen exerts its effect on bone in vivo is still unknown. To study if estrogen acts on bone directly, we used an experimental model in which test substances are infused locally into rat femur trabecular bone. SpragueDawley rats weighing 150-160 g were ovariectomized (OVX) and 14 days later a polyethylene tube (1 mm in diameter) connected to an Alzet osmotic minipump was implanted into the distal femur 9 mm from the joint. 17fiE2 (24 pl/day at 0.01-1 nM), 17a-estradiol (17aE2) (24 pl/day at 1 nM), or phosphatebuffered saline (NaCl, 8 g/liter; KCI, 0.2 g/liter; KH2PO4, 0.2 g/liter; Na2HPO4-7H2O, 2.16 g/liter) was infused for 8 days.The contralateral limb remained intact. Animals were sacrificed and bones were examined by histomorphometry. Ovariectomy caused a 50% loss in trabecular bone volume (TBV) in the secondary spongiosa (from 20.3% ± 1.7% to 9.6% + 1.1%; mean ± SEM), a 2-fold increase in osteoclast number (to 4.0 ± 0.4 per mm), a 3-fold increase in relative resorption surfaces (to 24.8% ± 2.9%), a 9-fold increase in osteoblast number (to 11.3 ± 2.1 per mm), and an 8-fold increase in relative osteoid surface (to 9.6% ± 1.7%). The local infusion of 17fiE2 for 8 days into OVX rats (t) restored the TBV dose dependently to 75% and 85% of control (non-OVX) levels, at 0.1 nM and 1 nM 17(3E2, respectively; (it) decreased osteoclast number and the relative resorption surface to control (non-OVX) levels; and (iii) further increased osteoblast number and the relative osteoid surface dose dependently (by 5-fold at 1 nM 173E2). Phosphate-buffered saline infusion was without effect.Infusion of 17ciE2 had no effect on TBV, osteoclast number, or resorption surface but increased slightly the osteoblast number and the osteoid surface. Its potency was 1/100 that of 1713E2. The local infusion of 17fiE2 or 17aE2 had no effect on body or uterine weight. We conclude from these rmdings that estrogen delivered directly to the bone of OVX rats in vivo at 2.4 and 24 fmol/day acted locally to inhibit bone resorption and stimulate bone formation.About 50 years ago, Albright et al.(1) suggested a link between postmenopausal osteoporosis and estrogen deficiency. The lack of estrogen is associated with increased bone remodeling rates, accelerated bone loss, and a negative calcium balance (2). Estrogen replacement therapy decreases bone turnover and the rate ofbone resorption and reduces the occurrence of fractures in postmenopausal osteoporosis. However, the mechanism by which estrogen exerts its effects on bone is still unknown (3,4 2172The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…The mechanism of action of E on bone is uncertain despite studies over the past three decades reporting effects on bone in rodents and quail and on mineral metabolism in humans (1)(2)(3)(4)(5)(20)(21)(22)(23)(24)(25)(26)(27)(28). The studies in rodents and quail have found effects of exogenous estrogens on osteoblasts, their precursors, or both (20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

“…The studies in rodents and quail have found effects of exogenous estrogens on osteoblasts, their precursors, or both (20)(21)(22)(23)(24)(25)(26)(27)(28). Endosteal proliferation and metaphyseal sclerosis were observed in several studies, implying an anatomic localization of the estrogen effect.…”

Section: Discussionmentioning

confidence: 99%

17 beta-estradiol acts directly on the clonal osteoblastic cell line UMR106.

Gray¹,

Flynn²,

Gray³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

166

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We studied the effect of 17f8-estradiol (E) on the proliferation and alkaline phosphatase activity of cultured UMR106 cells, a clonal osteoblastic cell line. Growth rates were reduced and alkaline phosphatase activity was increased in cells incubated for 2 days in medium containing E (10-8 M). In contrast, E had no effect on the growth rates or alkaline phosphatase of a human fibroblastic cell line, S90E. The effect of E was not observed with low cell density or at confluence. 1,25-Dihydroxyvitamin D3 antagonized the response to E. Preincubation of the cells with dexamethasone, a potent inducer of differentiation, reversed the effect of E or 1,25-dihydroxyvitamin D3. These results indicate that cellular and/or extracellular factors such as cell density, the phase of the cell cycle, the state of differentiation, and the presence or absence of other steroids influenced the response of UMR106 cells to E. Serum was removed from the culture medium to minimize the effect of the steroids, growth factors, and nutrients present in serum. A striking stimulation of alkaline phosphatase by E occurred with serum-free conditions. This stimulation was biphasic over an E concentration from 101-2 to 10-8 M, with the peak response at 10-1' M. The action of E on UMR106 cells was metabolite-specific, since the isomer 17a-estradiol produced no effect on proliferation rates or alkaline phosphatase activity. The cyclic AMP response to parathyroid hormone (residues 1-34) was not altered by E treatment of these cells. In contrast, dexamethasone exposure did increase the cyclic AMP response to parathyroid hormone. These results demonstrate a direct effect of E on an osteoblastic cell line. They also raise the possibility that similar or identical actions of E occur in cultured normal osteoblasts.Estrogens influence the skeleton, as evidenced by the loss of bone density in postmenopausal women (1, 2) and the preventative action of exogenous estrogens on the loss of bone density in ovariectomized subjects (3). Estrogen administration also produces changes related to bone and mineral metabolism, such as increased intestinal absorption of calcium (4) and alterations in the circulating calciotropic hormones (4, 5). The mechanism of estrogens' action on the skeleton is still unknown. Most investigators have postulated an indirect pathway because of the apparent absence of estrogen receptors in bone (6-9). We report the results of experiments showing an effect of 17p-estradiol (E) on the UMR106 cell line, a well-characterized osteoblastic cell model (10-12). MATERIALS AND METHODSMaterials. The culture media and additives were obtained from the Tissue Culture Facility of the Lineberger Cancer Research Center, University of North Carolina. The additives included fetal bovine serum, penicillin, streptomycin, insulin, transferrin, selenium, and trypsin, the latter for release of adherent cells. E and 17a-estradiol (17a-E) and dexamethasone were purchased from Sigma. Parathyroid hormone, as the synthetic fragment consisting of amino acid res...

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Cytology and autoradiography of estrogen-induced differentiation of avian endosteal cells

Cited by 41 publications

References 19 publications

Bone‐cell changes in estrogen‐induced bone‐mass increase in mice: Dissociation of osteoclasts from bone surfaces

Bone‐cell changes in estrogen‐induced bone‐mass increase in mice: Dissociation of osteoclasts from bone surfaces

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

17 beta-estradiol acts directly on the clonal osteoblastic cell line UMR106.

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