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1.  Exploratory factor analysis of the Oral Health Impact Profile 
Journal of oral rehabilitation  2014;41(9):635-643.
Although oral health-related quality of life (OHRQoL) as measured by the Oral Health Impact Profile (OHIP) is thought to be multidimensional, the nature of these dimensions is not known. The aim of this report was to explore the dimensionality of the OHIP using the Dimensions of OHRQoL (DOQ) Project, an international study of general population subjects and prosthodontics patients. Using the project's Learning Sample (N=5,173), we conducted an exploratory factor analysis on the 46 OHIP items not specifically referring to dentures for 5,146 subjects with sufficiently complete data. The first eigenvalue (27.0) of the polychoric correlation matrix was more than ten times larger than the second eigenvalue (2.6), suggesting the presence of a dominant, higher-order general factor. Follow-up analyses with Horn's parallel analysis revealed a viable second-order, four-factor solution. An oblique rotation of this solution revealed four highly correlated factors that we named Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact. These four dimensions and the strong general factor are two viable hypotheses for the factor structure of the OHIP.
PMCID: PMC4138231  PMID: 24909881
Oral health-related quality of life; Oral Health Impact Profile; dimensions; factor structure; exploratory factor analysis
2.  Confirmatory factor analysis of the Oral Health Impact Profile 
Journal of oral rehabilitation  2014;41(9):644-652.
Previous exploratory analyses suggest that the Oral Health Impact Profile (OHIP) consists of four correlated dimensions and that individual differences in OHIP total scores reflect an underlying higher-order factor. The aim of this report is to corroborate these findings in the Dimensions of Oral Health-Related Quality of Life (DOQ) Project, an international study of general population subjects and prosthodontics patients. Using the project's Validation Sample (N=5,022), we conducted confirmatory factor analyses in a sample of 4,993 subjects with sufficiently complete data. In particular, we compared the psychometric performance of three models: a unidimensional model, a four-factor model, and a bifactor model that included one general factor and four group factors. Using model fit criteria and factor interpretability as guides, the four-factor model was deemed best in terms of strong item loadings, model fit (RMSEA=0.05, CFI=0.99), and interpretability. These results corroborate our previous findings that four highly correlated factors—which we have named Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact —can be reliably extracted from the OHIP item pool. However, the good fit of the unidimensional model and the high inter-factor correlations in the four-factor solution suggest that OHRQoL can also be sufficiently described with one score.
PMCID: PMC4138269  PMID: 24909797
Oral health-related quality of life; Oral Health Impact Profile; dimensions; factor structure; confirmatory factor analysis
3.  Factor Analyses of the Oral Health Impact Profile - Overview and studied population 
A desideratum of oral health-related quality of life (OHRQoL) instruments - such as the Oral Health Impact Profile (OHIP) - is that they accurately reflect the structure of the measured construct(s). With this goal in mind, the Dimensions of Oral Health-Related Quality of Life (DOQ) Project was proposed to investigate the number and nature of OHRQoL dimensions measured by OHIP. In this report, we describe our aggregate data set for the factor analyses in the project, which consists of responses to the 49-item OHIP from general population subjects and prosthodontics patients from 6 countries, including a large age range of adult subjects and both genders.
Material and methods
The DOQ Project's aggregate data set combines data from 35 individual studies conducted in Croatia, Germany, Hungary, Japan, Slovenia, and Sweden.
The combined data set includes 10,778 OHIPs from 9,348 individuals (N=6,349 general population subjects, N=2,999 prosthodontic patients). To elucidate the OHIP latent structure, the aggregated data were split into a Learning Sample (N=5,173) for exploratory analyses and a Validation Sample (N=5,022) for confirmatory analyses. Additional data (N=583) were assigned to a third data set.
The Dimensions of Oral Health-Related Quality of Life Project contains a large amount of international data and is representative of populations where OHIP is intended to be used. It is well-suited to assess the dimensionality of the questionnaire.
PMCID: PMC4024446  PMID: 24440578
Oral Health Impact Profile; Factor analysis; questionnaire; general population; prosthodontic patients
4.  Effects of antibody to receptor activator of nuclear factor κ-B ligand on inflammation and cartilage degradation in collagen antibody-induced arthritis in mice 
Rheumatoid arthritis (RA) is an inflammatory disease that leads to destruction of both articular cartilage and bone tissues. In rheumatic joints, synoviocytes and T-lymphocytes as well as bone cells produce the receptor activator of nuclear factor κ-B (RANK) ligand (RANKL), which binds to RANK on the surface of osteoclasts and their precursor cells to induce differentiation and activation of osteoclasts. Hence, inhibition of RANKL may be a promising approach to suppress osteolysis in RA. On the other hand, RANKL production by lymphocytes indicates the possibility that its inhibition would be effective to suppress inflammation in RA. In addition, it has been reported that cathepsin K, a predominant cysteine protease in osteoclasts, is involved in cartilage destruction in RA model mice. Here, we evaluated the effects of an anti-RANKL antibody on inflammation in footpads and degradation of articular cartilage in RA model mice.
We induced arthritis in mice by injection of anti-type II collagen antibodies and lipopolysaccharide (LPS). Inhibition of RANKL by an anti-RANKL antibody (OYC1, Oriental Yeast, Tokyo, Japan) was confirmed by increased bone volume in the metaphysis of tibias. Swelling in either limb until day 14 was seen in 5 of 6 mice injected with anti-collagen antibodies and LPS without treatment with OYC1, while that was seen in 4 of 5 mice treated with OYC1. The average arthritis scores on day 14 in those groups were 2.17 and 3.00, respectively, indicating that OYC1 did not ameliorate inflammation in the limbs. Histological analyses indicated that OYC1 does not protect articular cartilage from destruction in mice with arthritis.
Our present study failed to show the effectiveness of an anti-RANKL antibody to ameliorate inflammation in the limbs or protect articular cartilage from degradation in a collagen antibody-induced arthritis mouse model.
Electronic supplementary material
The online version of this article (doi:10.1186/s12952-014-0018-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4272563  PMID: 25495344
Rheumatoid arthritis; Collagen antibody-induced arthritis; RANKL; Antibody; Inflammation; Articular cartilage
5.  BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation 
PLoS ONE  2013;8(6):e68774.
Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation, while it inhibits myogenic differentiation in C2C12 cells. To evaluate genes involved in BMP-2-induced osteoblast differentiation, we performed cDNA microarray analyses to compare BMP-2-treated and -untreated C2C12 cells. We focused on Alx3 (aristaless-like homeobox 3) which was clearly induced during osteoblast differentiation. Alx3, a homeobox gene related to the Drosophilaaristaless gene, has been linked to developmental functions in craniofacial structures and limb development. However, little is known about its direct relationship with bone formation. In the present study, we focused on the mechanisms of Alx3 gene expression and function during osteoblast differentiation induced by BMP-2. In C2C12 cells, BMP-2 induced increase of Alx3 gene expression in both time- and dose-dependent manners through the BMP receptors-mediated SMAD signaling pathway. In addition, silencing of Alx3 by siRNA inhibited osteoblast differentiation induced by BMP-2, as showed by the expressions of alkaline phosphatase (Alp), Osteocalcin, and Osterix, while over-expression of Alx3 enhanced osteoblast differentiation induced by BMP-2. These results indicate that Alx3 expression is enhanced by BMP-2 via the BMP receptors mediated-Smad signaling and that Alx3 is a positive regulator of osteoblast differentiation induced by BMP-2.
PMCID: PMC3689002  PMID: 23825702
6.  R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts 
Cytotechnology  2012;64(3):331-339.
R848, also known as resiquimod, acts as a ligand for toll-like receptor 7 (TLR7) and activates immune cells. In this study, we examined the effects of R848 on differentiation, survival, and bone-resorbing function of osteoclasts. R848 inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) and human peripheral blood-derived monocytes induced by receptor activator of NF-κB ligand in a dose-dependent manner. In addition, it inhibited mouse osteoclast differentiation induced in cocultures of bone marrow cells and osteoblasts in the presence of dihydroxyvitamin D3 [1,25(OH)2D3]. However, R848 did not affect the survival or bone-resorbing activity of mouse mature osteoclasts. R848 also upregulated the mRNA expression levels of interleukin (IL)-6, IL-12, interferon (IFN)-γ, and inducible nitric oxide synthase in mouse BMMs expressing TLR7. IFN-β was consistently expressed in the BMMs and addition of neutralizing antibodies against IFN-β to the cultures partially recovered osteoclast differentiation inhibited by R848. These results suggest that R848 targets osteoclast precursors and inhibits their differentiation into osteoclasts via TLR7.
PMCID: PMC3386391  PMID: 22358541
R848; Resiquimod; Osteoclasts; Toll-like receptor; Cellular differentiation; Bone
7.  Downregulation of Carbonic Anhydrase IX Promotes Col10a1 Expression in Chondrocytes 
PLoS ONE  2013;8(2):e56984.
Carbonic anhydrase (CA) IX is a transmembrane isozyme of CAs that catalyzes reversible hydration of CO2. While it is known that CA IX is distributed in human embryonic chondrocytes, its role in chondrocyte differentiation has not been reported. In the present study, we found that Car9 mRNA and CA IX were expressed in proliferating but not hypertrophic chondrocytes. Next, we examined the role of CA IX in the expression of marker genes of chondrocyte differentiation in vitro. Introduction of Car9 siRNA to mouse primary chondrocytes obtained from costal cartilage induced the mRNA expressions of Col10a1, the gene for type X collagen α-1 chain, and Epas1, the gene for hypoxia-responsible factor-2α (HIF-2α), both of which are known to be characteristically expressed in hypertrophic chondrocytes. On the other hand, forced expression of CA IX had no effect of the proliferation of chondrocytes or the transcription of Col10a1 and Epas1, while the transcription of Col2a1 and Acan were up-regulated. Although HIF-2α has been reported to be a potent activator of Col10a1 transcription, Epas1 siRNA did not suppress Car9 siRNA-induced increment in Col10a1 expression, indicating that down-regulation of CA IX induces the expression of Col10a1 in chondrocytes in a HIF-2α-independent manner. On the other hand, cellular cAMP content was lowered by Car9 siRNA. Furthermore, the expression of Col10a1 mRNA after Car9 silencing was augmented by an inhibitor of protein kinase A, and suppressed by an inhibitor for phosphodiesterase as well as a brominated analog of cAMP. While these results suggest a possible involvement of cAMP-dependent pathway, at least in part, in induction of Col10a1 expression by down-regulation of Car9, more detailed study is required to clarify the role of CA IX in regulation of Col10a1 expression in chondrocytes.
PMCID: PMC3575511  PMID: 23441228
8.  Oral health in the Japan self-defense forces - a representative survey 
BMC Oral Health  2011;11:14.
The oral health of military populations is usually not very well characterized compared to civilian populations. The aim of this study was to investigate two physical oral health characteristics and one perceived oral health measure and their correlation in the Japan self-defense forces (JSDF).
Number of missing teeth, denture status, and OHRQoL as evaluated by the Japanese 14-item version of the Oral Health Impact Profile (OHIP-J14) as well as the correlation between these oral health measures was investigated in 911 personnel in the JSDF.
Subjects did not have a substantial number of missing teeth and only 4% used removable dentures. The mean OHIP-J14 score was 4.6 ± 6.7 units. The magnitude of the correlation between the number of missing teeth with OHIP-J14 scores was small (r = 0.22, p < 0.001). Mean OHIP-J14 scores differed between subjects with and without dentures (8.6 and 4.4, p < 0.001).
Compared to Japanese civilian populations, personnel of the JSDF demonstrated good oral health. Two physical oral health characteristics were associated with perceived oral health.
PMCID: PMC3100240  PMID: 21501526
9.  Association between perceived chewing ability and oral health-related quality of life in partially dentate patients 
One of the most immediate and important functional consequences of many oral disorders is a reduction in chewing ability. The ability to chew is not only an important dimension of oral health, but is increasingly recognized as being associated with general health status. Whether perceived chewing ability and oral health-related quality of life (OHRQoL) are correlated to a similar degree in patient populations has been less investigated. The aim of this study was to examine whether perceived chewing ability was related to OHRQoL in partially dentate patients.
Consecutive partially dentate patients (N = 489) without signs or symptoms of acute oral disease at Tokyo Medical and Dental University's Prosthodontic Clinic participated in the study (mean age 63.0 ± 11.5, 71.2% female). A 20-item chewing function questionnaire (score range 0 to 20) was used to assess perceived chewing ability, with higher scores indicating better chewing ability. The 14-item Oral Health Impact Profile-Japanese version (OHIP-J14, score range 0 to 56) was used to measure OHRQoL, with higher scores indicating poorer OHRQoL. A Pearson correlation coefficient was calculated to assess the correlation between the two questionnaire summary scores. A linear regression analysis was used to describe how perceived chewing ability scores were related to OHRQoL scores.
The mean chewing function score was 12.1 ± 4.8 units. The mean OHIP-J14 summary score was 13.0 ± 9.1 units. Perceived chewing ability and OHRQoL were significantly correlated (Pearson correlation coefficient: -0.46, 95% confidence interval [CI]: -0.52 to -0.38), indicating that higher chewing ability was correlated with lower OHIP-J14 summary scores (p < 0.001), which indicate better OHRQoL. A 1.0-unit increase in chewing function scores was related to a decrease of 0.87 OHIP-J14 units (95% CI: -1.0 to -0.72, p < 0.001). The correlation between perceived chewing ability and OHRQoL was not substantially influenced by age and number of teeth, but by gender, years of schooling, treatment demand and denture status.
Patients' perception of their chewing ability was substantially related to their OHRQoL.
PMCID: PMC2974665  PMID: 20955614
10.  Validating an alternate version of the chewing function questionnaire in partially dentate patients 
BMC Oral Health  2009;9:9.
The aim of this study was to investigate the dimensionality, reliability, and validity of an alternate version of the chewing function questionnaire in partially dentate patients in Japan.
Subjects were partially dentate patients who attended the prosthodontic clinic at Tokyo Medical and Dental University (N = 491, 71% women, mean age (± SD): 63.0 ± 11.5 years). The questionnaire asked each subject to rate his or her ability to chew 20 common Japanese foods. For each individual, responses were combined to yield a chewing function summary score, with higher scores indicating better self-reported chewing ability. We used exploratory factor analysis to investigate the scores' dimensionality. For validity assessment, we computed the correlations between the chewing function score and oral health-related quality of life (OHRQoL, as measured by the Japanese 14-item Oral Health Impact Profile (OHIP-14)) Internal consistency of scores and test-retest reliability were investigated by asking a subset of subjects (N = 62) to complete the questionnaire twice, 2 weeks apart.
Exploratory factor analysis provided some evidence that self-reported chewing ability can be characterized by a summary score as the original authors suggest. Support for the validity of chewing function scores using the alternate version of the questionnaire was derived from correlations with OHIP-14 scores (r = -0.46, 95% confidence interval (CI): -0.53 to -0.39); thus, better chewing ability was associated with less impaired OHRQoL. Internal consistency was 'satisfactory,' with a Cronbach's alpha of 0.90 (lower limit of 95% CI: 0.89). The test-retest reliability was 'good,' with an intraclass correlation coefficient of 0.69 (95% CI: 0.56 to 0.82).
The alternate version of the chewing function questionnaire can be used as a stand-alone instrument because of the demonstrated reliability and validity of scores obtained using the questionnaire in partially dentate patients.
PMCID: PMC2667387  PMID: 19291293

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