Osteoclast growth factor activity in medium conditioned by fetal rat bones

Scheven, Ben A.; Hamilton, Nicola J.; Duncan, Alexander; Robins, Simon P.

doi:10.1016/0169-6009(91)90024-t

Cited by 6 publications

(7 citation statements)

References 32 publications

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“…Typically, rapid 1,25D effects such as transcaltachia in the intestinal epithelium (17) and insulin secretion by ␤-pancreatic cells (18,19) have been studied at the tissue level. In osteoblasts, the bone-forming cells, 1,25D stimulates the production of bone matrix proteins that are constitutively secreted to the extracellular matrix (20,21). The 1,25D hormone has multiple modulatory effects on the electrical activity of several ion channel types present in the osteoblast plasma membrane, where it acts through different molecular mechanisms, which may include the participation of cytoplasmic second messengers and a putative membrane receptor molecule (22).…”

mentioning

confidence: 99%

Rapid modulation of osteoblast ion channel responses by 1α,25(OH) ₂ -vitamin D ₃ requires the presence of a functional vitamin D nuclear receptor

Zanello

Norman²

2004

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

143

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1␣,25(OH)2-Vitamin D3 (1,25D) modulates osteoblast gene expression of bone matrix proteins via a nuclear vitamin D receptor (VDR) and also modifies the electrical state of the plasma membrane through rapid nongenomic mechanisms still not fully understood. The physiological significance of 1,25D membrane-initiated effects remains unclear. To elucidate whether the VDR is required for 1,25D-promoted electrical responses, we studied 1,25D modulation of ion channel activities in calvarial osteoblasts isolated from VDR knockout (KO) and WT mice. At depolarizing potentials, Cl ؊ currents were significantly potentiated (13.5 ؎ 1.6-fold increase, n ‫؍‬ 12) by 5 nM 1,25D in VDR WT but not in KO (0.96 ؎ 0.3 fold increase, n ‫؍‬ 11) osteoblasts. L-type Ca 2؉ currents significantly shift their peak activation by ؊9.3 ؎ 0.7 mV (n ‫؍‬ 10) in the presence of 5 nM 1,25D in VDR WT but not in KO cells, thus facilitating Ca 2؉ influx. Furthermore, we found that 1,25D significantly increased wholecell capacitance in VDR WT (⌬Cap ‫؍‬ 2.3 ؎ 0.4 pF, n ‫؍‬ 8) but not in KO osteoblasts (⌬Cap ‫؍‬ 0.3 ؎ 0.1 pF, n ‫؍‬ 8); this corresponds to a rapid (1-2 min) fusion in WT of 71 ؎ 33 versus in KO only 9 ؎ 6 individual secretory granules. We conclude that, in calvarial osteoblasts, 1,25D modulates ion channel activities only in cells with a functional VDR and that this effect is coupled to exocytosis. This is a demonstration of the requirement of a functional classic steroid receptor for the rapid hormonal modulation of electric currents linked to secretory activities in a target cell.N ongenomic responses to the steroid 1␣,25(OH) 2 -vitamin D 3 (1,25D) develop at the plasma membrane of various target cells and comprise rapid (seconds to minutes) changes in ion channel activities, activation of second messenger pathways, and elevation of cytosolic calcium concentrations (1-3). At a different level, 1,25D regulates the expression of tissue-specific genes via a nuclear vitamin D receptor (VDR) that functions as a transcription factor (4, 5). Although these two mechanisms of action are known to occur through different signaling pathways, there is no clear consensus yet whether rapid, membrane-related actions of 1,25D are initiated by a unique membrane receptor of unknown molecular identity or whether the classic VDR is involved (6-9).In bone, 1,25D elicits physiological responses at both the genomic and nongenomic levels. Osteoblasts, which are secretory cells, produce a variety of bone matrix proteins and actively participate in the mineralization process under the influence of hormones involved in mineral metabolism, such as 1,25D. Recently, several strains of functional VDR knockout (KO) mice have been created by means of deletion of selected portions of the VDR gene (10-13). They constitute a valuable tool for the study of a vast range of physiological conditions that arise from an impaired 1,25D physiology. Nuclear VDR KO mice, with abrogated 1,25D genomic actions, develop a genotype typical of rickets type II, characterized by decreased...

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mentioning

confidence: 99%

Rapid modulation of osteoblast ion channel responses by 1α,25(OH) ₂ -vitamin D ₃ requires the presence of a functional vitamin D nuclear receptor

Zanello

Norman²

2004

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

143

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“…The formation of mononuclear precursor cells committed to the osteoclast lineage as opposed to macrophage differentiation also requires the presence of other specific osteoclastopoietic factors (7,19,27,28). Our finding that neutralizing M-CSF activity did not inhibit differentiation of mononuclear TRAP-positive cells implies that additional (RCCM-derived) soluble factor(s) other than M-CSF are important in the differentiation process of osteoclast precursors.…”

Section: Kinetics Of Osteoclast Induction After 4 Days Preculturementioning

confidence: 66%

“…Oursler and Osdody showed that avian bone released a soluble factor into the culture medium that promoted avian osteoclast-like cell formation (14). Our work showed previously that RCCM contained a so-called "Osteoclast Growth Factor" (OGF) activity that stimulated osteoclast-like cell formation in serum-free cultures of rat bone marrow and long bone cuhures (19). OGF activity was not characterized by direct "bone resorbing stimulating activity," and could not be blocked by specific antibodies against M-CSF and GM-CSF (4,19).…”

Section: Kinetics Of Osteoclast Induction After 4 Days Preculturementioning

confidence: 89%

“…Calvaria from 19-d-old rat fetuses were cultured in petri dishes containing serum-free, 0.1% BSA supplemented MEM as described previously (19). Rat calvaria CM (RCCM) was collected daily over a 4-d period, and each time replaced with fresh medium.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, the presence ofstromal or osteoblastic cells appears to be required to provide an inductive "feeder" layer enabling osteoclast generation and functional activity through cell-cell contacts (26,27). Nonetheless, accumulating evidence indicates that osteoclast-like ceils can develop in the absence of stromal-like ceils, and that soluble factors or eytokines may induce osteoclast differentiation independently (4,7,9,11,12,14,15,17,19).…”

Section: Introductionmentioning

confidence: 95%

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A sequential culture approach to study osteoclast differentiation from nonadherent porcine bone marrow cells

Scheven¹,

Milne²,

Robins³

1998

In Vitro Cell.Dev.Biol.-Animal

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A "sequential culture step" system was devised to study osteoclast differentiation from newborn porcine bone marrow cells. Nonadherent cells were collected from cultures of bone marrow cells, and subsequently precultured at a low cell density in low-serum medium supplemented with L929-conditioned medium (L9-CM) derived M-CSF/CSF-1. After 4 d, adherent cells mainly composed of M-CSF-dependent macrophage/osteoclast progenitors, but devoid of stromal-like cells, were further cultured in medium supplemented with L9-CM and CM derived from serum-free cultures of fetal rat calvarial bones. This phase was characterized by a rapid induction of mono- and multinucleated (pre)osteoclast-like cells, positive for cytochemical TRAP activity, but negative for nonspecific esterase (NSE) staining. The presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulated osteoclast generation, whereas calcitonin treatment significantly inhibited this process. The osteoclastic nature of the cells was confirmed by the occurrence of extensive, characteristic bone resorption on dentin slices, which was associated with release of type I collagen N-telopeptides from the bone matrix into the culture medium. The presence of a DNA synthesis inhibitor (HU) during the first 3 d of culture completely inhibited osteoclast formation, whereas HU treatment during the last phase did not affect production of multinucleated osteoclast-like cells. Likewise, a specific antibody directed against M-CSF during the first preculture period, completely abolished osteoclast formation. Adding the antibody during the last phase of the culture, however, strongly inhibited multinucleated osteoclast formation, accompanied by a significant increase in a mononuclear TRAP-positive, NSE-positive (osteoclast precursor) cell fraction. These results indicate that M-CSF is essential for progenitor proliferation as well as for (pre)osteoclast maturation and/ or fusion into multinucleated cells, but also suggest that additional soluble (bone-derived) factors are involved as cofactors in the differentiation process to committed mononuclear osteoclast precursors. The porcine marrow culture approach provides a suitable model system to investigate specific soluble osteoclast-inducing factors affecting different stages of osteoclast development.

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Macrophage colony-stimulating factor restores bone resorption in op/op bone in vitro in conjunction with parathyroid hormone or 1,25-dihydroxyvitamin D3

Morohashi

Corboz

Fleisch

et al. 1994

Journal of Bone and Mineral Research

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The in vivo administration of macrophage colony-stimulating factor (M-CSF) restores osteoclastogenesis and bone resorption in the op/op murine osteopetrosis. In vitro, exogenous M-CSF has been shown to be necessary for the generation of osteoclast-like cells in cocultures of hematopoietic and mesenchymal cells obtained from this mutant. In this study we investigated the capacity of M-CSF and other cytokines and hormones, alone or in combination, to induce bone resorption in explants of op/op metatarsals and metacarpals prelabeled with 45Ca. The effect on bone resorption was verified by counting the number of osteoclasts generated in the mineralized matrix. No osteoclast formation and no bone resorption were observed in the absence of M-CSF. M-CSF alone had only a slight effect at the high concentration of 10(4) units/ml. Addition of PTH or 1,25-(OH)2D3 together with M-CSF induced both osteoclastogenesis and bone resorption. The release of 45Ca was linear with time up to 15 days. PTH or 1,25-(OH)2D3 could not be substituted by TNF-alpha or IL-1, whereas IL-6 had a weak effect. M-CSF could not be replaced by GM-CSF. This study further emphasizes the role of M-CSF, PTH, and 1,25-(OH)2D3 in osteoclastogenesis.

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Osteoclast growth factor activity in medium conditioned by fetal rat bones

Cited by 6 publications

References 32 publications

Rapid modulation of osteoblast ion channel responses by 1α,25(OH) ₂ -vitamin D ₃ requires the presence of a functional vitamin D nuclear receptor

Rapid modulation of osteoblast ion channel responses by 1α,25(OH) ₂ -vitamin D ₃ requires the presence of a functional vitamin D nuclear receptor

A sequential culture approach to study osteoclast differentiation from nonadherent porcine bone marrow cells

Macrophage colony-stimulating factor restores bone resorption in op/op bone in vitro in conjunction with parathyroid hormone or 1,25-dihydroxyvitamin D3

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Osteoclast growth factor activity in medium conditioned by fetal rat bones

Cited by 6 publications

References 32 publications

Rapid modulation of osteoblast ion channel responses by 1α,25(OH) 2 -vitamin D 3 requires the presence of a functional vitamin D nuclear receptor

Rapid modulation of osteoblast ion channel responses by 1α,25(OH) 2 -vitamin D 3 requires the presence of a functional vitamin D nuclear receptor

A sequential culture approach to study osteoclast differentiation from nonadherent porcine bone marrow cells

Macrophage colony-stimulating factor restores bone resorption in op/op bone in vitro in conjunction with parathyroid hormone or 1,25-dihydroxyvitamin D3

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Rapid modulation of osteoblast ion channel responses by 1α,25(OH) ₂ -vitamin D ₃ requires the presence of a functional vitamin D nuclear receptor

Rapid modulation of osteoblast ion channel responses by 1α,25(OH) ₂ -vitamin D ₃ requires the presence of a functional vitamin D nuclear receptor