Opg, Rank, and Rankl in Tooth Development: Co-ordination of Odontogenesis and Osteogenesis

2004 ◽  
Vol 83 (3) ◽  
pp. 241-244 ◽  
Author(s):  
A. Ohazama ◽  
J.-M. Courtney ◽  
P.T. Sharpe
Keyword(s):  
Tooth Development ◽  
Nuclear Factor Κb ◽  
Cellular Interactions ◽  
Rankl Expression ◽  
Dental Papilla ◽  
Spatiotemporal Expression ◽  
Receptor Activator ◽  
Explant Cultures ◽  
Enamel Epithelium ◽  
Tooth Germs

Osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) are mediators of various cellular interactions, including bone metabolism. We analyzed expression of these three genes during murine odontogenesis from epithelial thickening to cytodifferentiation stages. Opg showed expression in the thickening and bud epithelium. Expression of Opg and Rank was observed in both the internal and the external enamel epithelium as well as in the dental papilla mesenchyme. Although Rankl expression was not detected in tooth epithelium or mesenchyme, it was expressed in pre-osteogenic mesenchymal cells close to developing tooth germs. All three genes were detected in developing dentary bone at P0. The addition of exogenous OPG to explant cultures of tooth primordia produced a delay in tooth development that resulted in reduced mineralization. We propose that the spatiotemporal expression of these molecules in early tooth and bone primordia cells has a role in co-ordinating bone and tooth development.

Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis

2011 ◽  
Vol 71 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Maria J H Boumans ◽  
Rogier M Thurlings ◽  
Lorraine Yeo ◽  
Dagmar Scheel-Toellner ◽  
Koen Vos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Osteoclast Precursors ◽  
Receptor Activator ◽  
Hands And Feet

ObjectivesTo examine how rituximab may result in the inhibition of joint destruction in rheumatoid arthritis (RA) patients.MethodsTwenty-eight patients with active RA were treated with rituximab. Radiographs of hands and feet before and 1 year after therapy were assessed using the Sharp–van der Heijde score (SHS). Expression of bone destruction markers was evaluated by immunohistochemistry and immunofluorescence of synovial biopsies obtained before and 16 weeks after the initiation of treatment. Serum levels of osteoprotegerin, receptor activator of nuclear factor κB ligand (RANKL), osteocalcin and cross-linked N-telopeptides of type I collagen (NTx) were measured by ELISA before and 16 weeks post-treatment.ResultsAfter 1 year, the mean (SD) change in total SHS was 1.4 (10.0). Sixteen weeks after treatment there was a decrease of 99% in receptor activator of nuclear factor κB-positive osteoclast precursors (p=0.02) and a decrease of 37% (p=0.016) in RANKL expression in the synovium and a trend towards reduced synovial osteoprotegerin expression (25%, p=0.07). In serum, both osteoprotegerin (20%, p=0.001) and RANKL (40%, p<0.0001) levels were significantly reduced 16 weeks after treatment, but the osteoprotegerin/RANKL ratio increased (157%, p=0.006). A trend was found towards an increase of osteocalcin levels (p=0.053), while NTx concentrations did not change.ConclusionsRituximab treatment is associated with a decrease in synovial osteoclast precursors and RANKL expression and an increase in the osteoprotegerin/RANKL ratio in serum. These observations may partly explain the protective effect of rituximab on the progression of joint destruction in RA.

scholarly journals Role of Prostaglandin E in Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Osteoblasts Induced by Cell Adhesion to Bone Marrow B-lymphocytes

2009 ◽  
Vol 55 (5) ◽  
pp. 832-837 ◽  
Author(s):  
Michiko Hirata ◽  
Suguru Harada ◽  
Chiho Matsumoto ◽  
Morichika Takita ◽  
Chisato Miyaura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
B Lymphocytes ◽  
Nuclear Factor Κb ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Receptor Activator

scholarly journals Colony-Stimulating Factor-1 (CSF-1) Directly Inhibits Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression by Osteoblasts

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 4977-4988 ◽  
Author(s):  
Y. Wittrant ◽  
Y. Gorin ◽  
S. Mohan ◽  
B. Wagner ◽  
S. L. Abboud-Werner
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Colony Stimulating Factor ◽  
Wild Type ◽  
Rankl Expression ◽  
Nadph Oxidase Activity ◽  
Rankl Mrna ◽  
Receptor Activator ◽  
Bone Marrow Cultures ◽  
Stimulating Factor

Colony-stimulating factor-1 (CSF-1), released by osteoblasts, stimulates the proliferation of osteoclast progenitors via the c-fms receptor (CSF-1R) and, in combination with receptor activator of nuclear factor-κB ligand (RANKL), leads to the formation of mature osteoclasts. Whether the CSF-1R is expressed by osteoblasts and mediates specific biological effects in osteoblasts has not been explored. Wild-type primary calvaria osteoblasts (OB) were analyzed for CSF-1R expression (RT-PCR and Western blot) and functionality (immunocomplex kinase assay). OB were serum starved for 24 h, and the effect of CSF-1 (0–100 ng/ml) on OB biological activities was determined at 48 h. In wild-type mouse bone marrow cultures, CSF-1 was tested for its effect on RANKL mRNA and osteoclast formation. Because ROS influence osteoblast RANKL expression, studies analyzed the effect of CSF-1 on reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and Nox1 and Nox4 proteins. Results indicate that OB express CSF-1R mRNA and protein and that CSF-1R could be phosphorylated in the presence of CSF-1. In osteoblasts, CSF-1 decreased RANKL mRNA in a dose- and time-dependent manner. Incubation of bone marrow cultures with CSF-1 resulted in a significant decline in tartrate-resistant acid phosphatase (TRACP) activity and CTR expression. RANKL-decreased expression by CSF-1 was correlated with a decrease of NADPH oxidase activity as well as Nox1 and Nox4 protein levels. These findings provide the first evidence that osteoblasts express CSF-1R and are a target for CSF-1 ligand. CSF-1-mediated inhibition of RANKL expression on osteoblasts may provide an important mechanism for coupling bone formation/resorption and preventing excessive osteoclastogenesis during normal skeletal growth.

scholarly journals Expression of Phosphate Transporters during Dental Mineralization

2017 ◽  
Vol 97 (2) ◽  
pp. 209-217 ◽  
Author(s):  
L. Merametdjian ◽  
S. Beck-Cormier ◽  
N. Bon ◽  
G. Couasnay ◽  
S. Sourice ◽  
...  
Keyword(s):  
Tooth Development ◽  
Human Tooth ◽  
Direct Role ◽  
Spatiotemporal Expression ◽  
Tooth Mineralization ◽  
Dentin Mineralization ◽  
Polymerase Chain ◽  
Tooth Germs ◽  
Dental Mineralization

The importance of phosphate (Pi) as an essential component of hydroxyapatite crystals suggests a key role for membrane proteins controlling Pi uptake during mineralization in the tooth. To clarify the involvement of the currently known Pi transporters (Slc17a1, Slc34a1, Slc34a2, Slc34a3, Slc20a1, Slc20a2, and Xpr1) during tooth development and mineralization, we determined their spatiotemporal expression in murine tooth germs from embryonic day 14.5 to postnatal day 15 and in human dental samples from Nolla stages 6 to 9. Using real-time polymerase chain reaction, in situ hybridization, immunohistochemistry, and X-gal staining, we showed that the expression of Slc17a1, Slc34a1, and Slc34a3 in tooth germs from C57BL/6 mice were very low. In contrast, Slc34a2, Slc20a1, Slc20a2, and Xpr1 were highly expressed, mostly during the postnatal stages. The expression of Slc20a2 was 2- to 10-fold higher than the other transporters. Comparable results were obtained in human tooth germs. In mice, Slc34a2 and Slc20a1 were predominantly expressed in ameloblasts but not odontoblasts, while Slc20a2 was detected neither in ameloblasts nor in odontoblasts. Rather, Slc20a2 was highly expressed in the stratum intermedium and the subodontoblastic cell layer. Although Slc20a2 knockout mice did not show enamel defects, mutant mice showed a disrupted dentin mineralization, displaying unmerged calcospherites at the mineralization front. This latter phenotypical finding raises the possibility that Slc20a2 may play an indirect role in regulating the extracellular Pi availability for mineralizing cells rather than a direct role in mediating Pi transport through mineralizing plasma cell membranes. By documenting the spatiotemporal expression of Pi transporters in the tooth, our data support the possibility that the currently known Pi transporters may be dispensable for the initiation of dental mineralization and may rather be involved later during the tooth mineralization scheme.

Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Hepatocellular Carcinoma With Bone Metastasis

2006 ◽  
Vol 14 (3) ◽  
pp. 1191-1199 ◽  
Author(s):  
Atsushi Sasaki ◽  
Kenji Ishikawa ◽  
Naotsugu Haraguchi ◽  
Hiroshi Inoue ◽  
Tetsuya Ishio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bone Metastasis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Receptor Activator

scholarly journals Targeted Deletion of a Distant Transcriptional Enhancer of the Receptor Activator of Nuclear Factor-κB Ligand Gene Reduces Bone Remodeling and Increases Bone Mass

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 146-153 ◽  
Author(s):  
Carlo Galli ◽  
Lee A. Zella ◽  
Jackie A. Fretz ◽  
Qiang Fu ◽  
J. Wesley Pike ◽  
...  
Keyword(s):  
Bone Mass ◽  
Bone Remodeling ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Transcriptional Enhancer ◽  
Dihydroxyvitamin D3 ◽  
Rankl Mrna ◽  
Receptor Activator ◽  
Stimulation Of

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast differentiation, and hormones and cytokines that stimulate bone resorption increase RANKL expression in stromal/osteoblastic cells. We have previously shown that PTH and 1,25-dihydroxyvitamin D3 control murine RANKL gene expression in vitro, in part, via an evolutionarily conserved transcriptional enhancer, designated the distal control region (DCR), located 76 kb upstream from the transcription start site. Herein we describe the phenotype of mice lacking this enhancer. Deletion of the DCR reduced PTH and 1,25-dihydroxyvitamin D3 stimulation of RANKL mRNA and osteoclast formation in primary bone marrow cultures as well as stimulation of RANKL mRNA in bone. DCR deletion also reduced basal RANKL mRNA levels in bone, thymus, and spleen. Moreover, mice lacking the DCR exhibited increased bone mass and strength. The increase in bone mass was due to reduced osteoclast and osteoblast formation leading to a low rate of bone remodeling similar to that observed in humans and mice with hypoparathyroidism. These findings demonstrate that hormonal control of RANKL expression via the DCR is a critical determinant of the rate of bone remodeling.

Sign in / Sign up

Export Citation Format

Share Document