scholarly journals Inhibition of RANKL and Sema4d Improves Residual Ridge Resorption in Mice.

Author(s):  
Meri Hisamoto ◽  
Shunsuke Kimura ◽  
Kai Iwata ◽  
Toshihiko Iwanaga ◽  
Atsuro Yokoyama

Abstract Residual ridge resorption (RRR) is a chronic and progressive bone resorption following tooth loss. It causes deterioration of the oral environments and leads to the pathogenesis of various systemic diseases. However, the molecular mechanisms and risk factors for RRR progression are still unclear and controversial. In this study, we developed a tooth extraction model using mice for analyzing long-term morphological and gene expression changes in the alveolar bone. We further applied ovariectomy to this model to elucidate the effects of osteoporosis on RRR progression. As a result, the alveolar bone loss was biphasic and consisted of rapid loss in the early stages and subsequently slow and sustained bone loss over a long period. Gene expression analysis indicated that ovariectomy increased the expression of pro-inflammatory cytokines in the alveolar bone and prolonged the activation of osteoclasts same as histological analysis. Furthermore, the expressions of Tnfsf11 and Sema4d kept increasing for a long time in OVX mice. Administration of neutralization antibodies for receptor activator of NF-κB ligand (RANKL) effectively suppressed RRR. Similarly, inhibition of Semaphorin 4d (Sema4d) also improved alveolar bone loss. This study demonstrated that osteoporosis is a risk factor for RRR and that RANKL and Sema4d suppression are potential treatments.

2019 ◽  
Vol 46 (8) ◽  
pp. 799-808 ◽  
Author(s):  
Paula Tegelberg ◽  
Tellervo Tervonen ◽  
Matti Knuuttila ◽  
Jari Jokelainen ◽  
Sirkka Keinänen‐Kiukaanniemi ◽  
...  

1990 ◽  
Vol 61 (7) ◽  
pp. 434-437 ◽  
Author(s):  
Cynthia A. Layport ◽  
George W. Greco ◽  
Walter T. McFall

2017 ◽  
Vol 20 (4) ◽  
pp. 42 ◽  
Author(s):  
Daniela Martins de Souza ◽  
Alan De Aquino Silva ◽  
Kauê Alberto Pereira ◽  
Vitor Sulz Gonsalves ◽  
Vinicius Anéas Rodrigues ◽  
...  

<p><strong>Objective:</strong> The aim of the present study was to assess the effect of regular and constant long-term alcohol consumption on the percentage of the remaining periodontal bone support (PBS) and periodontal bone loss (PBL) in adult rats. <strong>Material and Methods: </strong>Fifty-four (54) rats were divided into 3 groups: Control (daily water intake, n=18) daily alcohol intake (20% ethanol, n=18) and social alcohol intake (20% ethanol 2x a week, n=18). The rats were treated with continuous free-choice access to both ethanol consumption frequencies. They were euthanized after 90 days and their left mandibles were radiographed for PBS measuring. The same left mandibles were defleshed and stained. The PBL was morphometrically assessed by measuring the distance between cement-enamel junction and alveolar bone crest. <strong>Results: </strong>Did not show difference (p &gt; 0.05) in the amount of consumed alcohol between the social and daily intake groups. Rats also evidenced lower PBS percentage and higher PBL (p&lt;0.05) in both alcohol consumption groups in comparison to the control. <strong>Conclusion: </strong>The long-term constant and regular same amount alcohol consumption may cause alveolar bone loss and reduce the remaining periodontal bone support in adult rats. Thus, the alveolar bone loss was associated with the amount of consumed alcohol, rather than with periodicity in periodontitis-free rats.</p><p><strong>Keywords</strong></p><p>Alveolar Bone Loss; Alcoholism; Ethanol; Periodontal Disease; X-ray.<strong></strong></p><p> </p>


2016 ◽  
Vol 782 ◽  
pp. 89-97 ◽  
Author(s):  
Yuki Arai ◽  
Kazuhiro Aoki ◽  
Yasuhiro Shimizu ◽  
Yasuhiko Tabata ◽  
Takashi Ono ◽  
...  

2016 ◽  
Vol 2 (2) ◽  
pp. 179-186 ◽  
Author(s):  
E.K. Kaye ◽  
P. Vokonas ◽  
R.I. Garcia

The relationship between bone mineral density and tooth loss in men is unclear. The aim of this retrospective cohort study was to determine if relative metacarpal bone area (MCA) predicts tooth loss in a cohort of 273 male participants in the Dental Longitudinal Study and Normative Aging Study of the Department of Veterans Affairs. Outer and inner cortical bone widths of the middle metacarpal of the nondominant hand were measured on anteroposterior hand radiographs approximately 11 y apart. Baseline MCA was computed and categorized into quartiles. The men were followed from 1971 to 2015. Incident tooth loss during 2 intervals was examined: concurrent with the MCA measurements and long term over the total follow-up (17 ± 7 y). Radiographic alveolar bone loss (ABL) was measured on periapical radiographs as a percentage of the distance from the cementoenamel junction to root apex, and the number of teeth with ABL >40% was computed. Negative binomial generalized linear regression models estimated the mean number of teeth with ABL >40% and the number lost (concurrent and total), controlling for age, smoking, number of teeth at baseline, percentage teeth with ≥1 decayed/filled surface, and years of follow-up. At baseline, MCA was inversely related to number of teeth with >40% ABL. Men in the lowest MCA quartile (Q1) lost the most teeth, both concurrent with MCA measurements and long term, but the association differed by caries level (≤55% or >55% decayed/filled teeth). At the low caries level, the numbers lost in Q1 were 29% greater than in the highest MCA quartile (Q4). At the high caries level, the numbers lost in Q1 were more than twice those in Q4. Associations were attenuated when further controlled for number of teeth with ABL>40%. These findings suggest that systemic bone status plays a role in tooth loss and that the association may be mediated by alveolar bone loss. Knowledge Transfer Statement: Low relative metacarpal bone area was related to loss of alveolar bone and incident tooth loss in men. This information extends previous research, primarily studies of women, showing that osteoporosis adversely affects oral health. Knowledge of a patient’s systemic bone status may be important for managing his or her periodontal disease. Tooth loss in the absence of periodontal inflammation may signify systemic bone loss. Interprofessional communication is central to maintaining optimal oral and bone health.


2004 ◽  
Vol 72 (8) ◽  
pp. 4471-4479 ◽  
Author(s):  
G. T. Hart ◽  
D. J. Shaffer ◽  
S. Akilesh ◽  
A. C. Brown ◽  
L. Moran ◽  
...  

ABSTRACT Periodontal disease is one of the most prevalent chronic inflammatory diseases. There is a genetic component to susceptibility and resistance to this disease. Using a mouse model, we investigated the progression of alveolar bone loss by gene expression profiling of susceptible and resistant mouse strains (BALB/cByJ and A/J, respectively). We employed a novel and sensitive quantitative real-time PCR method to compare basal RNA transcription of a 48-gene set in the gingiva and the spleen and the subsequent changes in gene expression due to Porphyromonas gingivalis oral infection. Basal expression of interleukin-1 beta (Il1b) and tumor necrosis factor alpha (Tnf) mRNA was higher in the gingiva of the susceptible BALB/cByJ mice than in the gingiva of resistant A/J mice. Gingival Il1b gene expression increased further and Stat6 gene expression was turned on after P. gingivalis infection in BALB/cByJ mice but not in A/J mice. The basal expression of interleukin-15 (Il15) in the gingiva and the basal expression of p-selectin (Selp) in the spleen were higher in the resistant A/J mice than in the susceptible BALB/cByJ mice. In the resistant A/J mice the expression of no genes detectably changed in the gingiva after infection. These results suggest a molecular phenotype in which discrete sets of differentially expressed genes are associated with genetically determined susceptibility (Il1b, Tnf, and Stat6) or resistance (Il15 and Selp) to alveolar bone loss, providing insight into the genetic etiology of this complex disease.


2014 ◽  
Vol 93 (11) ◽  
pp. 1095-1100 ◽  
Author(s):  
Y. Zhang ◽  
L. Wei ◽  
R.J. Miron ◽  
Q. Zhang ◽  
Z. Bian

Semaphorin 4d (Sema4d) has been proposed as a novel target gene for the treatment of osteoporosis. Recently, we fabricated a site-specific bone-targeting system from polymeric nanoparticles that demonstrates an ability to prevent bone loss in an osteoporotic model by interfering with Sema4d gene expression using small interference RNA (siRNA) molecules. The aim of the present investigation was to determine the effects of this targeting system on the periodontium, an area of high bone turnover. We demonstrated, by single photon emission computed tomography, that intravenous injection of this molecule in ovariectomized Balb/C mice is able to target alveolar bone peaking 4 hr post-injection. We then compared, by histological analysis, the bone volume/total volume (BV/TV), alveolar bone height loss, immunohistochemical expression of Sema4d, and total number of osteoclasts in mandibular alveolar bone. Four treatment modalities were compared as follows: (1) sham-operated, (2) OVX-operated, (3) OVX+estrogen replacement therapy, and (4) OVX+siRNA-Sema4d animals. The results from the present study demonstrate that an osteoporotic condition significantly increases alveolar bone height loss, and that the therapeutic effects via bone-targeting systems featuring interference of Sema4d are able to partly counteract alveolar bone loss caused by osteoporosis. While the future therapeutic demand for the large number of patients suffering from osteoporosis faces many challenges, we demonstrate within the present study an effective drug-delivery moiety with anabolic effects on the bone remodeling cycle able to locate and target alveolar bone regeneration.


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