Quantitative relationship between osteoclasts, osteoclast nuclei and the extent of the resorbing surface in hamster periodontal disease

Makris, Georgios; Saffar, Jean‐Louis

doi:10.1016/0003-9969(82)90104-2

Cited by 31 publications

(29 citation statements)

References 24 publications

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“…Osteoclasts generally acquire more nuclei, containing an average of 5–20 nuclei, and become larger by fusing with other multinuclear osteoclasts or with mononuclear osteoclast precursors . However, the osteoclasts derived from some diseased tissues are increased both in number and size, and can be huge and have a large number of nuclei.…”

Section: Discussionmentioning

confidence: 99%

Characterization of bone mineral‐resembling biomaterials for optimizing human osteoclast differentiation and resorption

Nakamura¹,

Hentunen²,

Salonen³

et al. 2013

J Biomedical Materials Res

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Bioresorption is a biological mechanism by which biomaterials are resorbed and thereby disappear from implantation sites partially or completely over a period of time. Osteoclast-medicated bioresorption is a possible new advantage to incorporate material degradation into remodeling in bone metabolism process. The purpose of this study was to investigate the osteoclastogenesis and bioresorption of synthesized calcium phosphate materials. Differentiation into mature human osteoclasts on carbonated hydroxyapatite (CA) was significantly enhanced compared to hydroxyapatite (HA) and β-tricalcium phosphate, based on the quantitative gene expressions of molecular markers for osteoclast differentiation. Osteoclasts adhered and differentiated into giant multinuclear TRAP-positive cells on every type of synthesized sample based on the histological analysis. Morphological observations using fluorescence and quantitative analysis revealed that the actin rings of osteoclasts on CA were thick, small in diameter and co-localized with vinculin, similar to the rings found on bone slices. In contrast, the actin rings of osteoclasts on HA and culture dishes were thin and large in diameter. Scanning electron microscopic images and quantitative analysis indicated that the resorption pits on CA were significantly deeper than those on HA due to the enhanced tight sealing ability between osteoclasts and their substrate.

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Section: Discussionmentioning

confidence: 99%

Characterization of bone mineral‐resembling biomaterials for optimizing human osteoclast differentiation and resorption

Nakamura¹,

Hentunen²,

Salonen³

et al. 2013

J Biomedical Materials Res

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“…As indicated by several in vivo and in vitro studies, large osteoclasts with 10 or more nuclei are more active bone resorbers than small osteoclasts with 5 or less nuclei. (48,(52)(53)(54) Other in vivo bone resorption parameters, the percentage of trabecular osteoclast surface to bone surface (Oc.S/BS, %) and the ratio of osteoclast number to bone surface (Oc.N/BS, N/mm) were also increased in transgenic mice compared with those in wildtype mice, which further confirmed the ability of BSP to increase osteoclastic activity and bone resorption in vivo.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Bone Sialoprotein Leads to an Uncoupling of Bone Formation and Bone Resorption in Mice

Valverde

Zhang

Fix

et al. 2008

Journal of Bone and Mineral Research

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ABSTRACT:The purpose of this study was to determine the effects of bone sialoprotein (BSP) overexpression in bone metabolism in vivo by using a homozygous transgenic mouse line that constitutively overexpresses mouse BSP cDNA driven by the cytomegalovirus (CMV) promoter. CMV-BSP transgenic (TG) mice and wildtype mice were weighed, and their length, BMD, and trabecular bone volume were measured. Serum levels of RANKL, osteocalcin, osteoprotegerin (OPG), TRACP5b, and PTH were determined. Bone histomorphometry, von Kossa staining, RT-PCR analysis, Western blot, MTS assay, in vitro mineralization assay, and TRACP staining were also performed to delineate phenotypes of this transgenic mouse line. Compared with wildtype mice, adult TG mice exhibit mild dwarfism, lower values of BMD, and lower trabecular bone volume. TG mice serum contained increased calcium levels and decreased PTH levels, whereas the levels of phosphorus and magnesium were within normal limits. TG mice serum also exhibited lower levels of osteoblast differentiation markers and higher levels of markers, indicating osteoclastic activity and bone resorption. H&E staining, TRACP staining, and bone histomorphometry showed that adult TG bones were thinner and the number of giant osteoclasts in TG mice was higher, whereas there were no significant alterations in osteoblast numbers between TG mice and WT mice. Furthermore, the vertical length of the hypertrophic zone in TG mice was slightly enlarged. Moreover, ex vivo experiments indicated that overexpression of BSP decreased osteoblast population and increased osteoclastic activity. Partly because of its effects in enhancing osteoclastic activity and decreasing osteoblast population, BSP overexpression leads to an uncoupling of bone formation and resorption, which in turn results in osteopenia and mild dwarfism in mice. These findings are expected to help the development of therapies to metabolic bone diseases characterized by high serum level of BSP.

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“…Under inflammatory conditions, such as rheumatoid arthritis and periodontal disease, OCs are larger and contain more nuclei compared to normal controls [Makris and Saffar, 1982;Takano et al, 2004]. We demonstrated that large OCs (10þ nuclei) have an increased expression of proteases, such as MMP9 and cathepsin K, and activating receptors, such as RANK, IL-1RI, and TNF-R1, whereas small OCs (2-5 nuclei) expressed higher levels of the decoy receptor IL-1RII [Trebec et al, 2007].…”

mentioning

confidence: 84%

VEGF‐A expression in osteoclasts is regulated by NF‐κB induction of HIF‐1α

Trebec-Reynolds

Voronov

Heersche

et al. 2010

J of Cellular Biochemistry

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Large osteoclasts (10+ nuclei), predominant in rheumatoid arthritis and periodontal disease, have higher expression of proteases and activating receptors and also have increased resorptive activity when compared to small (2-5 nuclei) osteoclasts. We hypothesized that large and small osteoclasts activate different signaling pathways. A Signal Transduction Pathway Finder Array was used to compare gene expression of large and small osteoclasts in RAW 264.7-derived osteoclasts. Expression of vascular endothelial growth factor A (Vegfa) was higher in large osteoclasts and this result was confirmed by RT-PCR. RT-PCR further showed that RANKL treatment of RAW cells induced Vegfa expression in a time-dependent manner. Moreover, VEGF-A secretion in conditioned media was also increased in cultures with a higher proportion of large osteoclasts. To investigate the mechanism of Vegfa induction, specific inhibitors for the transcription factors NF-kappaB, AP-1, NFATc1, and HIF-1 were used. Dimethyl bisphenol A, the HIF-1alpha inhibitor, decreased Vegfa mRNA expression, whereas blocking NF-kappaB, AP-1, and NFATc1 had no effect. Furthermore, the NF-kappaB inhibitor gliotoxin inhibited Hif1alpha mRNA expression. In conclusion, VEGF-A gene and protein expression are elevated in large osteoclasts compared to small osteoclasts and this increase is regulated by HIF-1. In turn, Hif1alpha mRNA levels are induced by RANKL-mediated activation of NF-kappaB. These findings reveal further differences in signaling between large and small osteoclasts and thereby identify novel therapeutic targets for highly resorptive osteoclasts in inflammatory bone loss.

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Quantitative relationship between osteoclasts, osteoclast nuclei and the extent of the resorbing surface in hamster periodontal disease

Cited by 31 publications

References 24 publications

Characterization of bone mineral‐resembling biomaterials for optimizing human osteoclast differentiation and resorption

Characterization of bone mineral‐resembling biomaterials for optimizing human osteoclast differentiation and resorption

Overexpression of Bone Sialoprotein Leads to an Uncoupling of Bone Formation and Bone Resorption in Mice

VEGF‐A expression in osteoclasts is regulated by NF‐κB induction of HIF‐1α

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