Journal ArticleDOI
Generation of osteoclasts from hemopoietic cells and a multipotential cell line in vitro
G. Hattersley,T.J. Chambers +1 more
TLDR
An assay for osteoclastic differentiation is developed in which bone marrow cells are incubated in liquid culture on slices of cortical bone and results are strong evidence that osteoclasts derive from the hemopoietic stem cell and suggest that bone marrow stroma possesses additional characteristics distinct from those that induce differentiation of other hemopOietic cells that are specifically required for osteclastic differentiation.Abstract:
Osteoclasts are the cells that resorb bone. It is generally presumed, on the basis of indirect experiments, that they are derived from the hemopoietic stem cell. However, this origin has never been established. We have developed an assay for osteoclastic differentiation in which bone marrow cells are incubated in liquid culture on slices of cortical bone. The bone slices are inspected in the scanning electron microscope after incubation for the presence of excavations, which are characteristic of osteoclastic activity. We have now incubated bone marrow cells at low density, or a factor-dependent mouse hemopoietic cell line (FDCP-mix A4) with 1,25 dihydroxyvitamin D3 (a hormone which we have previously found induces osteoclastic differentiation) with and without murine bone marrow stromal cells, or with and without 3T3 cells, on bone slices. Neither the bone marrow cells nor the bone marrow stromal cells alone developed osteoclastic function even in the presence of 1,25 dihydroxyvitamin D3. However, extensive excavation of the bone surface was observed, only in the presence of 1,25 dihydroxy-vitamin D3, on bone slices on which bone marrow stromal cells were cocultured with low-density bone marrow cells or the hemopoietic cell line. Similar results were obtained when the bone marrow stromal cells were killed by glutaraldehyde fixation; 3T3 cells were unable to substitute for stromal cells. These results are strong evidence that osteoclasts derive from the hemopoietic stem cell and suggest that although mature osteoclasts possess neither receptors for nor responsiveness to 1,25 dihydroxyvitamin D3, the hormone induces osteoclastic function through a direct effect on hemopoietic cells rather than through some accessory cell in the bone marrow stroma. The failure of 3T3 cells, which enable differentiation of other hemopoietic progeny from this cell line, to induce osteoclastic differentiation suggests that bone marrow stroma possesses additional characteristics distinct from those that induce differentiation of other hemopoietic cells that are specifically required for osteoclastic differentiation.read more
Citations
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Journal ArticleDOI
17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens.
G. Girasole,Robert L. Jilka,G. Passeri,S. Boswell,G. Boder,D.C. Williams,Stavros C. Manolagas,Stavros C. Manolagas +7 more
TL;DR: In vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
Journal ArticleDOI
Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts.
TL;DR: It is suggested that M-CSF continues to modulate osteoclastic activity once osteoclasts are on resorptive sites, through regulation of the balance between resorption and migration, such that not only the quantity, but the spatial pattern of Resorption can be controlled by adjacent M- CSF- secreting cells of osteoblastic lineage.
Journal ArticleDOI
Regulation of the differentiation and function of osteoclasts
TL;DR: A hypothesis is presented in which the osteoclast is a mononuclear phagocyte directed towards a debriding function by TGF‐β, activated for this function by TRANCE, and induced to become specifically osteoclastic by the characteristics of the substrate or signals from bone cells that betoken such characteristics.
Journal ArticleDOI
Enforced Expression of Bcl-2 in Monocytes Rescues Macrophages and Partially Reverses Osteopetrosis in op/op Mice
Eric Lagasse,Irving L. Weissman +1 more
TL;DR: It is proposed that M-CSF augments monocyte survival, permitting them to respond to internal and external cues for their differentiation, and shows significant replenishment of tissue macrophages in op/op hMRP8bcl-2 mice.
Journal ArticleDOI
Introduction to bone biology.
TL;DR: There are a significant number of cytokines, that are locally produced and may control bone resorption, that include prostaglandins, IL1, TNF alpha, possibily IL6, and so on.
References
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Journal ArticleDOI
Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis.
TL;DR: It is clearly demonstrate that the major sulphated glycosaminoglycan of mouse marrow stroma, heparan sulphate4, possesses the ability to adsorb both GM-CSF and the multilineage haemopoietic growth factor, Interleukin 3 (IL-3).
Journal ArticleDOI
Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment
TL;DR: It is reported that granulocyte-macrophage colony-stimulating activity can be eluted from culturedStromal layers and that exogenous GM-CSF binds to GAGs from bone marrow stromal ECM, which may be an important function of the marrow microenvironment and may be involved in haematopoietic cell regulation.
Book
The hemopoietic colony stimulating factors
TL;DR: It was not until the introduction in 1966 of methods for growing colonies of normal hemopoietic cells in semisolid culture, that progress was made in identifying and characterizing corresponding specific regulators for other hemopOietic populations.
Journal Article
Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption.
TL;DR: It is suggested that the TNF may exert a significant influence on osteoclastic bone resorption in vivo through a primary effect on osteoblastic cells, which are induced by TNF to produce a factor that stimulates osteoclastically resorptive cells.
Journal ArticleDOI
Osteoblastic cells mediate osteoclastic responsiveness to parathyroid hormone.
P. M. J. McSHEEHY,T.J. Chambers +1 more
TL;DR: The results indicate that PTH acts primarily on osteoblasts, which are induced by the presence of the hormone to stimulate osteoclastic bone resorption.