No 1,25-dihydroxyvitamin D3 receptors on osteoclasts of calcium-deficient chicken despite demonstrable receptors on circulating monocytes.

Merke, J.; Klaus, Günter; Hügel, Ulrike; Waldherr, R; Ritz, Eberhard

doi:10.1172/jci112292

Cited by 99 publications

(40 citation statements)

References 11 publications

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“…Receptors for 1,25(OH) 2 D 3 are ubiquitous, with the probable and paradoxical exception of the osteoclast (Merke et al 1986). The dependency of osteoclast induction by PTH on a response in stromal cells suggests that osteoclast-inductive capacity is not a constitutive function of these stromal cells but requires hormone induction.…”

Section: Osteoclast Induction By Pth · K Fuller and Others 345mentioning

confidence: 99%

Induction of osteoclast formation by parathyroid hormone depends on an action on stromal cells

Fuller

Owens²,

Chambers³

1998

Journal of Endocrinology

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It is believed that parathyroid hormone (PTH) increases the resorptive activity of pre-existing osteoclasts through a primary interaction with cells of the osteoblastic lineage. Much less is known, however, of the mechanisms by which PTH induces osteoclast formation. It is known that osteoclast formation occurs through a contact-dependent interaction between stromal cells and haemopoietic precursors, but it is not known whether PTH acts on stromal cells or precursors to induce osteoclast formation. To address this issue, we compared the ability of haemopoietic cultures to generate osteoclasts, identified as calcitonin receptor positive (CTRP) cells, and to resorb bone in response to PTH and 1,25(OH) 2 vitamin D 3 (1,25(OH) 2 D 3 ). We found that when murine haemopoietic tissues were incubated at densities sufficiently high to support haemopoiesis, both PTH and 1,25(OH) 2 D 3 induced bone resorption in bone marrow cells, but in cultures of haemopoietic spleen only 1,25(OH) 2 D 3 induced CTRP cells, and neither hormone induced bone resorption. To determine whether these differences were attributable to differences in stromal cells or haemopoietic precursors, lower densities of haemopoietic spleen cells were incubated on osteoblastic (UMR 106), splenic or bone marrow stromal cells. We found that the behaviour of the cocultures reflected the characteristics and origin of the stromal cells. Thus, the ability of both osteoblastic and splenic stromal cells to induce CTRP cells with 1,25(OH) 2 D 3 , while only osteoblastic cells induced osteoclasts with PTH, from the same precursors, suggests that the ability of PTH to induce osteoclastic differentiation cannot be attributed to a hormonal action on osteoclast precursors, but depends on a response in stromal cells.

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Section: Osteoclast Induction By Pth · K Fuller and Others 345mentioning

confidence: 99%

Induction of osteoclast formation by parathyroid hormone depends on an action on stromal cells

Fuller

Owens²,

Chambers³

1998

Journal of Endocrinology

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“…Cell suspensions (1.5 X I07 cells/ ml) obtained by trypsinization were homogenized in TED buffer, i.e., 10 mM Tris HCI, 1.5 mM EDTA, 2 mM DTT, 10 mM sodium molybdate, pH 7.4. Crude fractions and nuclear extracts were prepared as described elsewhere (7,10) and used for sucrose density-gradient analysis, binding studies, or DNA affinity chromatography.…”

Section: Assay Of Vdr Activitymentioning

confidence: 99%

“…Cell extracts were prepared as described elsewhere (7,10,20). In brief, cell suspensions (1.5 X 107 cells/ml) were homogenized in 0.4 M KTED buffer (TED buffer supplemented with 0.4 M KC1).…”

Section: Assay Of Vdr Activitymentioning

confidence: 99%

“…DNA cellulose chromatography. DNA cellulose was prepared from polymerized calfthymus DNA (type I, Sigma Chemical Co., St. Louis, MO) and cellulose (CG-l 1; Whatman Instruments, Clifton, NJ) as described earlier (7,10) and formed into small columns (2 ml (14, 15, 24) and to have profound effects on endothelial cell functions (16). VDR activity was therefore examined to determine if it is altered in BAEC stimulated by activators of PKC.…”

Section: Assay Of Vdr Activitymentioning

confidence: 99%

“…Abbreviations used in this paper: BAEC, bovine aortic endothelial cells; DiC8, sn-1,2-dioctanoylglycerol; MAb 9A7y2b, MAb against the Most, if not all, of the biological actions of 1,25(OH)2D3 are believed to be mediated by a high-affinity nuclear receptor (VDR) for the vitamin D hormone (2). Recent studies of cultured human promyelocytic leukemia cells (3), cultured human macrophages (4,5), skin cells (6,7) and other cells (8)(9)(10)(11)(12)) have disclosed several new biological functions of 1,25(OH)2D3. These studies indicate that 1,25(OH)2D3 plays potential roles in cell proliferation/differentiation (13) and also is biosynthesized in several ofits peripheral target cells (4)(5)(6) in addition to the traditional renal site of formation.…”

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Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries.

et al. 1989

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Because 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to play roles in both proliferation and differentiation of novel target cells, the potential expression of 1,25(OH)2D3 receptor (VDR) activity was investigated in cultured bovine aortic endothelial cells (BAEC). Receptor binding assays performed on nuclear extracts of BAEC revealed a single class of specific, high-affinity VDR that displayed a 4.5-fold increase in maximal ligand binding (Nm.x) in rapidly proliferating BAEC compared with confluent, density-arrested cells. When confluent BAEC were incubated with activators of protein kinase C (PKC), N., increased 2.5-fold within 6-24 h and this upregulation was prevented by sphingosine, an inhibitor of PKC, as well as by actinomycin D or cycloheximide. Immunohistochemical visualization using a specific MAb disclosed nuclear localized VDR in venular and capillary endothelial cells of human skin biopsies, documenting the expression of VDR, in vivo, and validating the BAEC model. Finally, additional experiments indicated that BAEC formed the 1,25(OH)2D3 hormonal metabolite from 25(OH)D3 substrate, in vitro, and growth curves of BAEC maintained in the presence of 10-8 M 1,25(OH)2D3 showed a 36% decrease in saturation density. These data provide evidence for the presence of a vitamin D microendocrine system in endothelial cells, consisting of the VDR and a la-hydroxylase enzyme capable of producing 1,25(OH)2D3. That both components of this system are coordinately regulated, and that BAEC respond to the 1,25(OH)2D3 hormone by modulating growth kinetics, suggests the existence of a vitamin D autocrine loop in endothelium that may play a role in the development and/or functions of this pathophysiologically significant cell population. Introduction It is well established that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)' is a crucial hormone in Ca2' homeostasis (1). (13) and also is biosynthesized in several ofits peripheral target cells (4-6) in addition to the traditional renal site of formation. Because endothelial cells are a dynamic tissue with spontaneous or injury-dependent cell renewal and expression of specific cell functions at the blood/vessel-wall interface, these cells were examined to determine whether they are potential targets for 1,25(OH)2D3. Initially, the possible presence of specific binding sites for 1,25(OH)2D3 was probed using cultured bovine aortic endothelial cells (BAEC) as a model. When receptors for 1,25(OH)2D3 were observed, the following hypotheses were tested: (a) that the growth state of BAEC may be associated with changes in VDR activity; (b) that BAEC differentiation induced by activators of protein kinase C (PKC) (14-17) may be associated with VDR regulation; (c) that growth parameters of BAEC may be altered in response to 1,25(OH)2D3; (d) that the receptor may be expressed in vivo in endothelial cells in venules and capillaries of human skin; and (e) that BAEC may possess la-hydroxylase activity to form the sterol hormone ligand for the receptor. These studies describe the ...

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Retinoic acid stimulates expression of the functional osteoclast integrin αvβ3: Transcriptional activation of the β3 but not the αv gene

et al. 1996

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The capacity of osteoclasts to resorb bone depends, in part, on the surface expression of the integrin alpha v beta 3. We have investigated whether the steroid hormone retinoic acid, known to stimulate bone resorption, regulates the appearance of the alpha v beta 3 complex in avian osteoclast presursors. Using surface labeling, followed by immunoprecipitation with a alpha v beta 3-specific antibody, we show that retinoic acid increases surface expression of the heterodimer in a dose- and time-dependent manner. Northern analysis reveals that the high basal steady-state levels of alpha v mRNA do not change, while those for beta 3 rise significantly from their initially low levels. Nuclear run-on studies confirm that steroid treatment stimulates transcription of the beta 3, but not the alpha v gene. Osteoclast precursors treated with retinoic acid exhibit increased multinucleation and expression of the osteoclast marker enzyme tartrate-resistant acid phosphatase. However, the fused cells do not have an increased capacity to resorb bone. In summary, multinucleated cells generated in this study do not represent fully differentiated bone-resorbing polykaryons. These results suggest that treatment of osteoclast precursors with retinoic acid is necessary, but insufficient, for expression of the mature osteoclast phenotype.

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No 1,25-dihydroxyvitamin D3 receptors on osteoclasts of calcium-deficient chicken despite demonstrable receptors on circulating monocytes.

Cited by 99 publications

References 11 publications

Induction of osteoclast formation by parathyroid hormone depends on an action on stromal cells

Induction of osteoclast formation by parathyroid hormone depends on an action on stromal cells

Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries.

Retinoic acid stimulates expression of the functional osteoclast integrin αvβ3: Transcriptional activation of the β3 but not the αv gene

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