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  • 1
    Electronic Resource
    Electronic Resource
    Bone Metastasis Can osteoclasts be excluded? (2007)
    [s.l.] : Nature Publishing Group
    Nature 445.2007, 7130, E19-, (1 S.) 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Arising from: D. H. Jones et al. Nature 440, 692–696 (2006); Jones et al. reply The RANK/RANKL signalling mechanism is the final common pathway of osteoclast formation and activity. Inhibitors of RANK ligand (RANKL) that bind ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nature05657
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  • 2
    Electronic Resource
    Electronic Resource
    Genetic ablation of parathyroid glands reveals another source of parathyroid hormone (2000)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 406 (2000), S. 199-203 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/35018111
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  • 3
    Electronic Resource
    Electronic Resource
    A skeleton key to metabolism (2007)
    [s.l.] : Nature Publishing Group
    Nature medicine 13 (2007), S. 1021-1023 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] A link between energy metabolism and bone has long been suspected but poorly defined. Obesity protects against osteoporosis, and maturity-onset (type 2) diabetes is associated with increased bone mineral density and fewer fractures. A direct link was made with the discovery that the ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm0907-1021
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  • 4
    Electronic Resource
    Electronic Resource
    Bone loss goes beyond estrogen (2006)
    [s.l.] : Nature Publishing Group
    Nature medicine 12 (2006), S. 612-613 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Since Fuller Albright suggested that osteoporosis was due to hormone deficiency at the menopause, simple sex-steroid deficiency has been considered the cause of bone loss. This has underpinned many approaches to prevention and treatment. A new possibility of higher control arises from a study by ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm0606-612
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  • 5
    Electronic Resource
    Electronic Resource
    Unidirectional migration of osteosarcoma cells with osteoblast characteristics in response to products of bone resorption (1982)
    Springer
    Calcified tissue international 34 (1982), S. 542-546 
    Details
    ISSN: 1432-0827
    Keywords: Osteoblast ; Chemotaxis ; Bone remodeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary To investigate the mechanisms by which bone-forming cells are attracted to areas of bone resorption during bone remodeling, we have usedin vitro methods to look for signals released by resorbing bone, which may be chemotactic for cultured bone cells. We have found that cultured rat osteosarcoma cells, which have characteristics associated with the osteoblastic phenotype, migrate in a unidirectional manner in response to a signal released by resorbing bones. These cells also migrated unidirectionally in response to Type I collagen, which comprises 95% of the bone matrix. This phenomenon of chemotaxis of bone-forming cells to sites of previous resorption may be an important component of the process of bone remodeling and the coupling of bone formation to bone resorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02411301
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  • 6
    Electronic Resource
    Electronic Resource
    Differential effects of transforming growth factor-β1 and bone morphogenetic protein 4 on gene expression and differentiated function of preosteoblasts (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 155 (1993), S. 112-119 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Transforming growth factor-β (TGF-β) and bone morphogenetic protein 4 (BMP 4) are both able, under certain circumstances, to induce endochondral bone formation in vivo. This study compared the effects of TGF-β and BMP 4 on the gene expression of a retinoic acid (RA) responsive rat clonal preosteoblast cell line, UMR 201, as well as the way in which these proteins interact with RA in these cells. Both similarities as well as differences between the effects and mechanism of action of TGF-β1 and BMP 4 were demonstrated. TGF-β1 (0.1 ng/ml) strongly induced matrix gla protein (MGP) mRNA and increased the steady state osteonectin (ON) mRNA level. Cotreatment with TGF-β1 and RA did not result in a further increase in MGP mRNA expression. In contrast, BMP 4 alone had no influence on MGP or ON mRNA expression but it significantly enhanced the RA induction of MGP mRNA. Pro-α(1) (l) collagen mRNA was increased by TGF-β1 (1 ng/ml) and BMP 4 (50 ng/ml). The addition of either TGF-β1 or BMP 4 together with RA resulted in a further increase in pro-α1(l) collagen mRNA levels. Both RA and TGF-β1, but not BMP 4, increased the transcriptional rate of the pro-α 1(l) collagen gene. TGF-β1 reduced the constitutive as well as RA-induced expression of osteopontin (OP) mRNA while BMP 4 reduced only the constitutive expression of OP mRNA. RA increased the transcriptional rate of the OP gene. Since the responses of UMR 201 cells to these structurally related factors were not identical, the results lend support to the concept that the coordinated expression of members of the TGF-β1 superfamily may be necessary to control the progression of specific cell types through their differentiation pathways. © 1993 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041550115
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  • 7
    Electronic Resource
    Electronic Resource
    Type I collagen substrate increases calcitonin and parathyroid hormone receptor-mediated signal transduction in UMR 106-06 osteoblast-like cells (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 156 (1993), S. 130-137 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Components of the extracellular matrices (ECM) exert pleiotropic effects in many cell systems, but little is known of the effect of ECM on hormone signal transduction. We have investigated the effect of ECM substrates on cell growth and signal transduction by calcitonin (CT) and parathyroid hormone (PTH) using the rat osteosarcoma cell line, UMR 106-06. Type I collagen (collagen[I]) and Matrigel changed the morphology of the cells and significantly inhibited cell growth by 37% or 23%, respectively, compared with control. None of laminin, fibronectin, or type IV collagen affected cell shape or proliferation. Cells cultured on collagen (I)-coated plates showed increased specific binding of labeled CT compared with cells on plastic plates. The effect was apparent by 24 h and persisted for at least 72 h. None of the other ECM affected CT binding. Scatchard analysis revealed that collagen(I) increased CT receptor numbers but not receptor affinity. Consistent with increased binding capacity, cells plated on collagen(I) had increased responses to each of CT and PTH in terms of cyclic adenosine monophosphate (cAMP) production compared to control cells. In addition, cAMP production by prostaglandin E2, cholera toxin, and forskolin was increased by 30-70% compared to control. These data suggest that collagen(I) had effects not only on membrane receptors but on guanosine triphosphate (GTP) binding proteins (G proteins). The effect of collagen(I) on CT binding was no longer present when the cells were freed from the plates by enzymatic dispersion and binding measured in cell suspensions. In UMR 106-01 cells transiently transfected with the porcine CT receptor cDNA, binding was similarly induced by collagen(I). These data are the first demonstration that collagen(I) may play an important role in signal transduction, affecting both receptors and G proteins in UMR 106-06 cells. These results draw attention to the potential role of the ECM of bone in hormone-induced responses. © 1993 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041560118
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  • 8
    Electronic Resource
    Electronic Resource
    Plasminogen-dependent activation of latent transforming growth factor beta (TGFβ) by growing cultures of osteoblast-like cells (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 157 (1993), S. 528-534 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Osteoblasts secrete transforming growth factor beta (TGFβ) as a biologically inert, latent complex that must be dissociated before the growth factor can exert its effects. We have examined the production and proteolytic activation of latent TGFβ (LTGFβ) by clonal UMR 106-01 rat osteosarcoma cells and neonatal mouse calvarial (MC) osteoblast-like cells in vitro. Synthetic bPTH-(1-34) increased the activity of tissue-type (tPA) and urokinase-type (uPA) plasminogen activators (PA) in cell lysates (CL) of UMR 106-01 cells. The concentration of active TGFβ in serum-free CM from cultures treated with bPTH-(1-34) and plasminogen was significantly greater than in CM from untreated controls and cultures treated with either bPTH-(1-34) or plasminogen alone. This effect occurred at concentrations of PTH-(1-34) that increased PA activity and was prevented by aprotinin, an inhibitor of plasmin activity. Treatment with bPTH-(1-34) had no effect on the concentration of TGFβ in acid-activated samples of CM. Functional consequences of proteolytically activated TGFβ was examined in primary cultures of neonatal MC osteoblast-like cells. Human platelet TGFβ1 caused a dose-dependent increase in the migration of these cells in an in vitro wound healing assay. Cell migration was also stimulated in cultures treated with bPTH-(1-34) and plasminogen together. This effect was blocked by an anti-TGFβ1 antibody. The results of these studies demonstrate that (1) LTGFβ secreted by osteoblasts in vitro is activated under conditions where the plasmin activity in the cultures is increased, and (2) the TGFβ generated by plasmin-mediated proteolysis is biologically active. We suggest that the local concentration of TGFβ in bone may be controlled by the osteoblast-associated plasminogen activator/plasmin system. Furthermore, since several calciotropic factors influence osteoblast PA activity, this system may have an important role in mediating their anabolic and/or catabolic effects. © 1993 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041570312
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  • 9
    Electronic Resource
    Electronic Resource
    Prostaglandin E2 regulates production of plasminogen activator isoenzymes, urokinase receptor, and plasminogen activator inhibitor-1 in primary cultures of rat calvarial osteoblasts (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 165 (1995), S. 521-529 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The bone resorbing agent, prostaglandin E2 (PGE2), was found to alter several components of the plasminogen activator (PA)/plasmin pathway in primary cultures of rat neonatal osteoblast-like cells. The mRNA and activities of both urokinase-type PA (uPA) and tissue-type PA (tPA) were enhanced by PGE2 treatment. The presence of mRNA for the uPA receptor (uPAR) has been demonstrated in these cells and steady-state levels shown to be greatly enhanced, the response being rapid and sustained for at least 24 hours. mRNA for plasminogen activator inhibitor 1 (PAI-1) was modulated in a biphasic manner, with inhibition of the constitutive level apparent at 4 hours of treatment and stimulation apparent at 12 hours and longer, while PAI-1 protein, measured by an ELISA assay for rat PAI-1, was diminished over this period. Neither PAI-2 mRNA nor mRNA for the broad spectrum protease inhibitor, protease nexin-1 (PN-1), was found to be modulated by PGE2. Therefore, PGE2 is likely to stimulate cell surface proteolytic activity, since uPA mRNA and cell-associated activity were elevated, as was mRNA for the cellular receptor for uPA. Although it was not possible to measure uPAR number and affinity it seems likely that elevated uPAR mRNA would translate into increased uPARs which would localize the increased uPA activity to the pericellular region. tPA mRNA and activity were also increased transiently with the activity inhibited with prolonged incubations, apparently by PAI-1. Elevation of tPA mRNA and activity may result in elevated activity within the extracellular matrix as tPA has been reported to associate with several matrix proteins. Thus the early effect of PGE2 would be to promote proteolysis, both pericellularly and in the extracellular matrix. The inhibition of PAI-1 mRNA and protein, which would contribute to the elevation of activity, is due to PGE2, but the later stimulatory effect on PAI-1 mRNA may be due to feedback regulation by transforming growth factor beta (TGFβ), secreted by osteoblasts and activated by elevated levels of PA. © 1995 Wiley-Liss Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041650310
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  • 10
    Electronic Resource
    Electronic Resource
    Cloning of an osteoblastic cell line involved in the formation of osteoclast-like cells (1990)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 145 (1990), S. 587-595 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Experiments have been carried out to determine the mechanisms involved in the formation of osteoclast-like cells from spleen cells in mice. Osteoclasts were defined as tartrate-resistan. acid phosphatase-positive multinucleated cells (TRACP-positive MNCs) in which specific calcitonin receptors were identified by autdradiography with labeled salmon calcitonin. Furthermore, cultures rich in these cells produced resorption pits when grown on dentine slices. Several clonal cell lines were obtained from fetal mouse calvariae and screened for their ability to induce TRACP-positive MNCs in response to 1α, 25-dihydroxyvitamin D3 “1α,25(OH)2D3” in co-cultures with spleen cells. A cell line, KS-4, was identified with the greatest potency in inducing osteolast-like cell formation in co-culture with spleen cells. The capacity of KS-4 cells to produce this effect was much greater than that of two bone marrow-derived stromal cell lines (MC3T3-G2/PA6 and ST2 cells), which we have previously shown to be effective in this system but to require treatment with dexamethasone in addition to 1α25(OH)2D3 (Udagawa et al.: Endocrinology 125:1805-1813, 1989). Parathyroid hormone (PTH) in creased cAMP production in KS-4 cells, and PTH and interleukin-1α also induced TRACP-positive MNCs in co-cultures with spleen cells. Contact between living KS-4 and spleen cells was necessary for osteoclast formation to take place, since this did not occur when the two populations were separated by a membrane filter, or when the KS-4 cells were killed by fixation. Separate cultures of either spleen cells or KS-4 cells formed no TRACP-positive MNCs. KS-4 cells synthesized predominantly type I collagen, formed bone nodules without added of β-glycerophosphate in a long-term culture, and expressed increasing alkaline phosphatase activity after confluence in culture. These results indicate that the KS-4 cells have properties consistent with progression toward the osteoblast phenotype, and represent a single cell line with the ability to promote osteoclast formation by a contact-requiring process.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041450327
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