Osteoblasts mediate the bisphosphonate inhibition on bone resorption through synthesis of an inhibitor of osteoclastic resorption

Bone ◽  
1995 ◽  
Vol 17 (6) ◽  
pp. 580 ◽  
Author(s):  
C. Vitté ◽  
H. Fleisch ◽  
H.L. Guenther
Keyword(s):  
Bone Resorption ◽  
Osteoclastic Resorption

scholarly journals Osteoblasts mediate interleukin 1 stimulation of bone resorption by rat osteoclasts.

1986 ◽  
Vol 164 (1) ◽  
pp. 104-112 ◽  
Author(s):  
B M Thomson ◽  
J Saklatvala ◽  
T J Chambers
Keyword(s):  
Bone Resorption ◽  
Interleukin 1 ◽  
Fold Increase ◽  
Osteoclastic Bone Resorption ◽  
Neonatal Rat ◽  
Osteoblastic Cells ◽  
Computer Assisted ◽  
Osteoclastic Resorption ◽  
Primary Action ◽  
Stimulation Of

A monocyte-derived factor with IL-1-like properties has recently been shown to cause resorption of bone in organ culture. We have investigated the action of IL-1 on disaggregated populations of osteoclasts, incubated alone or in the presence of osteoblastic cells, in an attempt to identify the target cell for IL-1 in bone, and to elucidate the mechanism by which IL-1 induces osteoclastic resorption. Osteoclasts were disaggregated from neonatal rat long bones and incubated on slices of human femoral cortical bone. Under these conditions, the majority of osteoclasts form distinctive excavations in the bone surface within 24 h, the volume of which can be quantified by computer-assisted morphometric and stereophotogrammetic techniques. IL-1 had no effect on bone resorption by osteoclasts alone, but when incubated in the presence of calvarial cells or cloned osteosarcoma cells, it induced a 3.8 (+/- 0.38)-fold increase in osteoclastic bone resorption, with significant enhancement at concentrations of greater than or equal to 30 pg/ml. The osteoblastic populations themselves did not resorb bone. The mechanism by which osteoblastic cells stimulate osteoclasts did not appear to depend upon PG synthesis; nor could we detect a diffusible substance in the medium of stimulated cocultures. These results indicate that IL-1 stimulates bone resorption through a primary action on osteoblasts, which are induced by IL-1 to transmit a short-range signal that stimulates osteoclastic bone resorption.

scholarly journals Cortisol mobilizes mineral stores from vertebral skeleton in the European eel: an ancestral origin for glucocorticoid-induced osteoporosis?

2009 ◽  
Vol 201 (2) ◽  
pp. 241-252 ◽  
Author(s):  
Miskal Sbaihi ◽  
Karine Rousseau ◽  
Sylvie Baloche ◽  
François Meunier ◽  
Martine Fouchereau-Peron ◽  
...  
Keyword(s):  
Bone Resorption ◽  
European Eel ◽  
Endocrine Regulation ◽  
Stimulatory Action ◽  
Bone Demineralization ◽  
Natural Bone ◽  
Ancestral Origin ◽  
Osteoclastic Resorption ◽  
Reproductive Migration ◽  
Stimulation Of

Endogenous excess cortisol and glucocorticoid (GC) therapy are a major cause of secondary osteoporosis in humans. Intense bone resorption can also be observed in other vertebrates such as migratory teleost fish at the time of reproductive migration and during fasting when large amounts of calcium and phosphate are required. Using a primitive teleost, the European eel, as a model, we investigated whether cortisol could play an ancestral role in the induction of vertebral skeleton demineralization. Different histological and histomorphometric methods were performed on vertebral samples of control and cortisol-treated eels. We demonstrated that cortisol induced a significant bone demineralization of eel vertebrae, as shown by significant decreases of the mineral ratio measured by incineration, and the degree of mineralization measured by quantitative microradiography of vertebral sections. Histology and image analysis of ultrathin microradiographs showed the induction by cortisol of different mechanisms of bone resorption, including periosteocytic osteolysis and osteoclastic resorption. Specificity of cortisol action was investigated by comparison with the effects of sex steroids. Whereas, testosterone had no effect, estradiol induced vertebral skeleton demineralization, an effect related to the stimulated synthesis of vitellogenin (Vg), an oviparous specific phospho-calcio-lipoprotein. By contrast, the cortisol demineralization effect was not related to any stimulation of Vg. This study demonstrates GC-induced bone demineralization in an adult non-mammalian vertebrate, which undergoes natural bone resorption during its life cycle. Our data suggest that the stimulatory action of cortisol on bone loss may represent an ancestral and conserved endocrine regulation in vertebrates.

Physical Examination and Radiographic Analysis to Detect Dental and Mandibular Bone Resorption in Cats: A Study of 81 Cases from Necropsy

1995 ◽  
Vol 12 (3) ◽  
pp. 97-100 ◽  
Author(s):  
William Gengler ◽  
Richard Dubielzig ◽  
Jan Ramer
Keyword(s):  
Bone Resorption ◽  
Physical Examination ◽  
Cortical Bone ◽  
Radiographic Analysis ◽  
Dental Calculus ◽  
Mandibular Bone ◽  
Osteoclastic Resorption

The mandibles of 81 randomly selected cats were examined clinically and radiographically for dental calculus, periodontitis, odontoclastic resorptive lesions (FORL) and osteoporosis. Extent of calculus increased with increasing age. Prevalence and severity of periodontitis and FORL increased with increasing age. Osteoclastic resorption and/or osteoporosis increased with age, advancing from rostral to caudal in cortical bone. No significant correlation of periodontitis with FORL could be demonstrated.

Localisation of mRNA for collagenase in osteocytic, bone surface and chondrocytic cells but not osteoclasts

1995 ◽  
Vol 108 (6) ◽  
pp. 2221-2230
Author(s):  
K. Fuller ◽  
T.J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Cells ◽  
In Situ Hybridisation ◽  
Cysteine Proteinases ◽  
Bone Surface ◽  
Matrix Metalloproteinase 1 ◽  
Osteoclastic Resorption ◽  
Stimulation Of

Osteoclasts resorb the extracellular matrix of bone by secreting protons and enzymes into a circumpherentially sealed compartment between the osteoclast and the bone surface. Although the lysosomal cysteine proteinases play a major role in matrix degradation by osteoclasts, collagenase (matrix metalloproteinase-1, EC 3.4.24.7) is also required for osteoclastic bone resorption, and may be directly involved in collagen degradation in the hemivacuole. We assessed the effects of inhibitors of cysteine proteinases and collagenase on bone resorption by osteoclasts isolated from rodent bone. We found that while inhibition of cysteine proteinases strongly suppressed osteoclastic resorption, inhibitors of collagenase were without effect on the number, size, or demineralised fringe of excavations. We could find no evidence of expression of mRNA for collagenase in rat osteoclasts by in situ hybridisation, but found that it was expressed by chondrocytes, bone surface cells and osteocytes adjacent to osteoclasts. The distribution of these cells, and the correlation between increased collagenase production and increased stimulation of osteoclastic resorption in vitro by bone cells, suggests that these cells might be involved in the regulation of bone resorption in situ, and that collagenase production might play a role in this process.

scholarly journals Diphyllin, a Novel and Naturally Potent V-ATPase Inhibitor, Abrogates Acidification of the Osteoclastic Resorption Lacunae and Bone Resorption

2007 ◽  
Vol 22 (10) ◽  
pp. 1640-1648 ◽  
Author(s):  
Mette G Sørensen ◽  
Kim Henriksen ◽  
Anita V Neutzsky-Wulff ◽  
Morten H Dziegiel ◽  
Morten A Karsdal
Keyword(s):  
Bone Resorption ◽  
Atpase Inhibitor ◽  
Osteoclastic Resorption

scholarly journals Acidification of the Osteoclastic Resorption Compartment Provides Insight into the Coupling of Bone Formation to Bone Resorption

2005 ◽  
Vol 166 (2) ◽  
pp. 467-476 ◽  
Author(s):  
Morten A. Karsdal ◽  
Kim Henriksen ◽  
Mette G. Sørensen ◽  
Jeppe Gram ◽  
Sophie Schaller ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Osteoclastic Resorption ◽  
Insight Into

scholarly journals Bone cells predispose bone surfaces to resorption by exposure of mineral to osteoclastic contact

1985 ◽  
Vol 76 (1) ◽  
pp. 155-165 ◽  
Author(s):  
T.J. Chambers ◽  
K. Fuller
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Mineral ◽  
Bone Cells ◽  
Mineral Dissolution ◽  
Osteoclastic Bone Resorption ◽  
Neonatal Rat ◽  
Adult Rat ◽  
Osteoclastic Resorption ◽  
Parietal Bones

The cell-free endocranial surface of young adult rat parietal bones was used as a substrate for osteoclastic bone resorption, either without prior treatment, or after incubation of the parietal bones with collagenase or neonatal rat calvarial cells. Untreated, the endocranial surface consisted of unmineralized organic fibres; incubation with calvarial cells or collagenase caused disruption and removal of these fibres, with extensive exposure of bone mineral on the endocranial surface, without morphologically detectable mineral dissolution. Neonatal rabbit osteoclasts resorbed bone to a greater extent from parietal bones pre-incubated with calvarial cells or collagenase than from untreated bones; mineral exposure and subsequent osteoclastic resorption were both increased if calvarial cells were incubated with parathyroid hormone; removal of bone mineral after incubation with calvarial cells removed the predisposition to osteoclastic resorption. These experiments demonstrate that calvarial cells are capable of osteoid destruction, and indicate that one mechanism by which osteoblasts induce osteoclastic bone resorption may be through digestion of the unmineralized organic material that covers bone surfaces, to expose the underlying resorption-stimulating bone mineral to osteoclastic contact.

scholarly journals Potent and Selective Cathepsin L Inhibitors Do Not Inhibit Human Osteoclast Resorptionin Vitro

2001 ◽  
Vol 276 (15) ◽  
pp. 11507-11511 ◽  
Author(s):  
Ian E. James ◽  
Robert W. Marquis ◽  
Simon M. Blake ◽  
Shing Mei Hwang ◽  
Catherine J. Gress ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Cathepsin L ◽  
Cathepsin K ◽  
Cysteine Proteases ◽  
Cathepsin Activity ◽  
Osteoclastic Resorption ◽  
Human Osteoclast

Cathepsins K and L are related cysteine proteases that have been proposed to play important roles in osteoclast-mediated bone resorption. To further examine the putative role of cathepsin L in bone resorption, we have evaluated selective and potent inhibitors of human cathepsin L and cathepsin K in anin vitroassay of human osteoclastic resorption and anin situassay of osteoclast cathepsin activity. The potent selective cathepsin L inhibitors (Ki= 0.0099, 0.034, and 0.27 nm) were inactive in both thein situcytochemical assay (IC50> 1 μm) and the osteoclast-mediated bone resorption assay (IC50> 300 nm). Conversely, the cathepsin K selective inhibitor was potently active in both the cytochemical (IC50= 63 nm) and resorption (IC50= 71 nm) assays. A recently reported dipeptide aldehyde with activity against cathepsins L (Ki= 0.052 nm) and K (Ki= 1.57 nm) was also active in both assays (IC50= 110 and 115 nm, respectively) These data confirm that cathepsin K and not cathepsin L is the major protease responsible for human osteoclastic bone resorption.

RANK ligand and TNF-α mediate acid-induced bone calcium efflux in vitro

2005 ◽  
Vol 289 (5) ◽  
pp. F1005-F1011 ◽  
Author(s):  
Kevin K. Frick ◽  
Kelly LaPlante ◽  
David A. Bushinsky
Keyword(s):  
Metabolic Acidosis ◽  
Bone Resorption ◽  
Acid Medium ◽  
Cell Receptor ◽  
Bone Cell ◽  
Calcium Efflux ◽  
Osteoclastic Resorption ◽  
Tnf Α ◽  
Simultaneous Inhibition

Chronic metabolic acidosis stimulates net calcium efflux from bone due to increased osteoclastic bone resorption and decreased osteoblastic collagen synthesis. Previously, we determined that incubation of neonatal mouse calvariae in medium simulating physiological metabolic acidosis leads to a significant, cyclooxygenase-dependent, increase in RNA for bone cell receptor activator of NF-κB ligand (RANKL) compared with incubation in neutral pH medium. In this study, we tested the hypothesis that the acid-mediated increase in RANKL expression is a primary mechanism for the stimulated osteoclastic resorption. Acid medium increased the medium concentration of sRANKL without altering the concentration of the decoy receptor osteoprotegerin (OPG). Inhibition of the RANKL pathway with concentrations of OPG up to 25 ng/ml, far greater than physiological, did not significantly decrease the robust acid-induced Ca efflux from bone nor did incubation of the calvariae with a different inhibitor, RANK/Fc (up to 50 ng/ml). Thus acid-induced net Ca efflux appears to involve mechanisms in addition to the RANK/RANKL pathway. Osteoblasts also produce TNF-α, another cytokine that stimulates the maturation and activity of osteoclasts. Incubation of calvariae in acid medium caused a significant increase in TNF-α levels. Incubation of calvariae with anti-TNF (up to 250 ng/ml) did not significantly decrease acid-induced net Ca efflux. However, the combination of RANK/Fc plus anti-TNF caused a significant but subtotal reduction in acid-induced Ca efflux, whereas the combination of RANK/Fc plus an isotype-matched control for the anti-TNF had no effect on Ca release. Thus simultaneous inhibition of RANKL and TNF-α is necessary to reduce acid-induced, cell-mediated net Ca efflux from bone; however, additional osteoblast-produced factors must also be involved in acid-induced, cell-mediated bone resorption.

scholarly journals GH/IGF-I and bone resorption in vivo and in vitro

2005 ◽  
Vol 152 (3) ◽  
pp. 327-332 ◽  
Author(s):  
Thor Ueland
Keyword(s):  
Bone Resorption ◽  
Normal Subjects ◽  
Beneficial Effects ◽  
Igf Receptors ◽  
Osteoclastic Resorption ◽  
Igf I ◽  
Systemic Factors ◽  
Osteoclast Function

IGF-I may act as one of several coupling agents by activating bone formation and bone resorption. In vivo studies in normal subjects, postmenopausal women and patients with excess or diminished GH production (acromegaly and GHD) indicate that both GH and IGF-I activate osteoclasts, but that GH has a more pronounced effect, independently of IGF-I. In vitro, GH and IGF receptors have been demonstrated on osteoclasts and both GH and IGF-I may directly modify osteoclast function and activity. In addition to direct effects on osteoclasts, GH and IGF-I may affect bone resorption indirectly by stimulating release of paracrine mediators that regulate osteoclastic resorption (cytokines). Critical for the bone resorptive process is the balance between OPG and RANKL, which is regulated by many systemic factors. In vivo and in vitro, GH/IGF-I may modulate this balance but these studies are difficult to interpret, reflecting the complexity of this system. Increased OPG expression may possibly protect against GH/IGF-I-induced bone resorption and potentially be important for the long-term beneficial effects of GH replacement. Further studies investigating the OPG/RANKL ratio and system in experimental and transgenic GH/IGF models may clarify these issues.

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