Menopause-Associated Changes in Mandibular Bone Microarchitecture Are Site-Specific.

BACKGROUND: There are conflicting reports on the effects of decreased estrogen levels on mandibular bone microarchitecture. Whether these effects are consistent throughout the mandible is unclear and may have important implications for treatment planning. PURPOSE: The goal of this study was to evaluate trabecular and cortical bone microstructure in the mandibular condyle and the mandibular basal bone and compare these sites between premenopausal and postmenopausal women. STUDY DESIGN, SETTING, SAMPLE: Participants were recruited for a cross-sectional cohort study at Columbia University Irving Medical Center. Each participant had cone-beam computed tomography taken of their mandibular condyles and the basal bone. Exclusion criteria for the population included a) current chemotherapy or immunotherapy; b) history of bisphosphonate or other osteoporosis therapy; and c) currently pregnant, nursing, or on hormonal birth control. INDEPENDENT VARIABLE: The predictor variables are menopausal status (before or after menopause) and mandibular region of interest (condyle/basal bone). MAIN OUTCOME VARIABLE: Parameters of interest included the following indicators of bone quality: trabecular bone volume fraction, trabecular thickness, trabecular number, trabecular separation, cortical bone volume fraction, cortical thickness, and cortical porosity. COVARIATES: Covariates included demographic variables such as age, estrogen levels, and ethnicity. ANALYSES: Quantitative microstructure analyses were conducted on cone-beam computed tomography images, and differences between groups for continuous measures (including age) were assessed with an unpaired t-test, and demographic variables were assessed by χ2. Statistical significance was recorded at P < .05. RESULTS: The premenopausal and postmenopausal groups each had 31 participants, with the following average age: premenopausal = 43.9 ± 6.9 versus postmenopausal = 57.5 ± 7.6 years old; P < .001, and estrogen levels: premenopausal = 91.77 ± 80.13 pg/ml versus postmenopausal = 41.44 ± 61.62 pg/ml; P < .01). Postmenopausal women had significantly greater condylar trabecular separation (0.61 ± 0.18 vs 0.47 ± 0.11 mm; P < .001) and lower trabecular number (1.03 ± 0.18 vs 1.21 ± 0.19 mm-1; P < .001) compared to premenopausal women. There were no significant differences in the basal bone microarchitectural parameters between the menopausal groups. CONCLUSION AND RELEVANCE: Menopause is associated with mandibular condylar trabecular bone loss but has minimal effects on the mandibular basal bone. This may have important ramifications for treatment planning in advanced-age individuals.

Postmenopausal women with HIV have increased tooth loss.

BACKGROUND: With effective antiretroviral therapy, people with HIV (PWH) are living longer and aging; the majority of PWH in the United States are now over the age of 50 and in women have gone through the menopause transition. Menopause potentiates skeletal bone loss at the spine, hip, and radius in PWH. The alveolar bone which surronds the teeth is different than long bones because it is derived from the neural crest. However, few studies have assessed the oral health and alveolar bone in middle aged and older women with HIV. Therefore, the objective of this study was to evaluate periodontal disease and alveolar bone microarchitecture in postmenopausal women with HIV. METHODS: 135 self-reported postmenopausal women were recruited (59 HIV-, 76 HIV + on combination antiretroviral therapy with virological suppression) from a single academic center. The following parameters were measured: cytokine levels (IFN-γ, TNF-α, IL-1ß, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17 A, OPG, and RANKL) in gingival crevicular fluid, bleeding on probing, probing depth, clinical attachment loss, number of teeth present, alveolar crestal height, and alveolar bone microarchitecture. RESULTS: The mean age of participants was 57.04+/-6.25 years and a greater proportion of women with HIV were black/African American (HIV + 68.42%, HIV- 23.73%; p < 0.001). There was no significant difference in bleeding on probing (p = 0.17) and attachment loss (p = 0.39) between women who were HIV infected vs. HIV uninfected. Women with HIV had significantly higher RANKL expression in Gingival Crevicular Fluid (HIV + 3.80+/-3.19 pg/ul, HIV- 1.29+/-2.14 pg/ul ; p < 0.001), fewer teeth present (HIV + 17.75+/-7.62, HIV- 22.79+/-5.70; p < 0.001), ), lower trabecular number (HIV + 0.08+/-0.01, HIV- 0.09+/-0.02; p = 0.004) and greater trabecular separation (HIV + 9.23+/-3.11, HIV- 7.99+/-3.23; p = 0.04) compared to women without HIV that remained significant in multivariate logistic regression analysis in a sub-cohort after adjusting for age, race/ethnicity, smoking status, and diabetes. CONCLUSION: Postmenopausal women with HIV have deterioration of the alveolar trabecular bone microarchitecture that may contribute to greater tooth loss.

Significance of radiographic temporomandibular degenerative joint disease findings.

The field of orthodontics has seen a recent increase in the number of patients over the age of 50 seeking treatment and also an increase in the use of cone beam technology. Similar to other joints in the body, the temporomandibular joint (TMJ) is associated with age-related degeneration. However, unlike other joints, degeneration of the TMJ is rarely symptomatic and when there is pain, it is usually self-limiting. In this article, we will review: a) the incidence and prevalence of TMJ degenerative diseases, b) similarities and differences of TMJ vs knee degenerative diseases, and c) current treatment recommendations for TMJ degenerative diseases. In the vast majority of people, radiographic evidence of TMJ degeneration is an incidental finding. Future longitudinal research is needed to follow the natural course of TMJ degenerative patients.

Evaluation of the mandibular condylar bone microarchitecture in people living with HIV.

OBJECTIVES: People living with HIV (PLWH) have been shown to have lower bone density at the spine, hip, and radius. However, whether a similar bone phenotype is seen in craniofacial bones is not known. The goal of this study was to evaluate the bone microarchitecture of the mandibular condyle in PLWH. METHODS: We recruited 212 participants, which included 88 HIV-negative participants and 124 PLWH on combination antiretroviral therapy with virological suppression from a single academic center. Each participant filled out a validated temporomandibular disorder (TMD) pain screening questionnaire and had cone beam computed tomography (CBCT) of their mandibular condyles. Qualitative radiographic evidence of temporomandibular joint disorders-osteoarthritis (TMJD-OA) assessment and quantitative microarchitecture analysis of their mandibular condylar bones were conducted. RESULTS: There was no statistically significant difference in either self-reported TMD or in radiographic evidence of TMJD-OA in PLWH compared with HIV-negative controls. Linear regression analysis revealed that positive HIV status remained significantly associated with increased trabecular thickness, decreased cortical porosity, and increased cortical bone volume fraction after adjusting for race, diabetes, sex, and age. CONCLUSION: PLWH have increased mandibular condylar trabecular bone thickness and cortical bone volume fraction compared with HIV-negative controls.

Estrogen signaling impacts temporomandibular joint and periodontal disease pathology.

Women experience a higher incidence of oral diseases including periodontal diseases and temporomandibular joint disease (TMD) implicating the role of estrogen signaling in disease pathology. Fluctuating levels of estrogen during childbearing age potentiates facial pain, high estrogen levels during pregnancy promote gingivitis, and low levels of estrogen during menopause predisposes the TMJ to degeneration and increases alveolar bone loss. In this review, an overview of estrogen signaling pathways in vitro and in vivo that regulate pregnancy-related gingivitis, TMJ homeostasis, and alveolar bone remodeling is provided. Deciphering the specific estrogen signaling pathways for individual oral diseases is crucial for potential new drug therapies to promote and maintain healthy tissue.

Extracellular Matrix Mediates BMP-2 in a Model of Temporomandibular Joint Osteoarthritis.

Temporomandibular joint (TMJ) osteoarthritis (OA) is a complex disease that affects both cartilage and subchondral bone. It is accompanied by loss of extracellular matrix (ECM) and may be controlled by bone morphogenetic protein-2 (BMP-2). We analyzed the effect of BMP-2 in both cartilage and subchondral bone in a TMJ-OA animal model that is deficient in biglycan (Bgn) and fibromodulin (Fmod) (Bgn-/-Fmod-/-). Whole mandibles were dissected from 3-week-old wild-type (WT) and Bgn-/-Fmod-/- mice and incubated with and without 250 µg/mL BMP-2 for 2 days using an explant culture system. Condyle growth was measured by microCT and the expression levels of cartilage and bone-related genes were analyzed using RT-PCR or by immunohistochemistry from condyles that contained an intact cartilage/subchondral bone interface. Osteoclast activity was estimated by tartrate-resistant acid phosphatase (TRAP) staining and by TRAP, Rankl, and Adamts4 mRNA expression levels. Our results showed that most parameters examined were slightly up-regulated in WT samples treated with BMP-2, and this up-regulation was significantly enhanced in the Bgn-/-Fmod-/- mice. The up-regulation of both catabolic and anabolic agents did not appear to positively affect the overall growth of Bgn-/-Fmod-/- condyles compared to WT controls. In summary, the up-regulation of both anabolic and catabolic genes in the WT and Bgn-/-Fmod-/- TMJs treated with BMP-2 suggests that BMP increases matrix turnover in the condyle, and, further, that Bgn and Fmod could have protective roles in regulating this process.

Effect of corticision and different force magnitudes on orthodontic tooth movement in a rat model.

INTRODUCTION: The aims of this study were to evaluate the effect of 2 distinct magnitudes of applied force with and without corticision (flapless corticotomy) on the rate of tooth movement and to examine the alveolar response in a rat model. METHODS: A total of 44 male rats (6 weeks old) were equally divided into 4 experimental groups based on force level and surgical intervention: light force, light force with corticision, heavy force, and heavy force with corticision. The forces were delivered from the maxillary left first molar to the maxillary incisors using prefabricated 10-g (light force) or 100-g (heavy force) nickel-titanium springs. The corticision procedure was performed at appliance placement and repeated 1 week later on the mesiopalatal aspect of the maxillary left first molars, with the right sides serving as the untreated controls. Microcomputed tomography was used to evaluate tooth movement between the maxillary first and second molars, and the alveolar response in the region of the maxillary first molar on day 14. Osteoclasts and odontoclasts were quantified, and the expression of receptor activator of nuclear factor kappa ß ligand was examined. RESULTS: Intragroup comparisons of bone volume fraction (BVF) and tissue density were found to be significantly less on the loaded sides, with the exception of BVF in the light force group. Intergroup comparisons evaluating magnitude of tooth movement, BVF, apparent density, and tissue density showed no significant differences. Histomorphometric analysis indicated that BVF was decreased in the light force group. No significant differences in the total numbers of osteoclasts and odontoclasts and the expression of receptor activator of nuclear factor kappa ß ligand were found between the groups. CONCLUSIONS: No differences in tooth movement or alveolar response were observed with microcomputed tomography based on force level or corticision procedure. A flapless surgical insult in the mesiopalatal aspect of the first molar with a single-site corticision was unable to induce clinical or histologic changes after 2 weeks of orthodontic tooth movement regardless of the force magnitude. Histologic analysis of the furcation area showed that light force significantly decreased BVF.

Men with HIV Have Increased Alveolar Bone Loss.

Background: Periodontal health in men with HIV remains understudied, despite suggestions of associations between HIV infection and gingival pocketing, periodontal attachment loss, and gingival inflammation. As antiretroviral therapy (ART) has improved the quality of life for people living with HIV (PLWH), aging-related risk factors and comorbidities, including periodontitis, have emerged. This study aims to assess alveolar bone height, gingival crevicular fluid (GCF) cytokines, and periodontal disease activity in men with and without HIV. Methods: Ninety-three men (50 HIV+, 43 HIV‒) aged 35-70 years were recruited from Columbia University Irving Medical Center clinics. Periodontal examination, GCF collection, and intraoral radiographs were conducted. Results: While no significant differences were observed in bleeding on probing, clinical attachment loss and pocket depths, men with HIV exhibited significantly greater alveolar crestal height on radiographs compared to men without HIV (HIV + 3.41+/-1.35 mm, HIV- 2.64+/-1.01 mm; p = 0.004), reflecting greater alveolar bone loss. GCF IL6 levels showed a trend towards elevation in men with HIV (HIV + 0.349+/-0.407 pg/ml, HIV- 0.220+/-0.228 pg/ml; p = 0.059). Conclusions: Men with HIV demonstrate increased alveolar bone loss compared to those without HIV, possibly mediated by elevated IL6 levels. These results underscore the importance of comprehensive oral health management in PLWH and highlight the need for further research understanding the mechanisms linking HIV infection, cytokine dysregulation, and periodontal health.

FGF Ligands and Receptors in Osteochondral Tissues of the Temporomandibular Joint in Young and Aging Mice.

OBJECTIVE: Fibroblast growth factors (FGFs) are a family of 22 proteins and 4 FGF receptors (FGFRs) that are crucial elements for normal development. The contribution of different FGFs and FGFRs for the homeostasis or disease of the cartilage from the mandibular condyle is unknown. Therefore, our goal was to characterize age-related alterations in the protein expression of FGF ligands and FGFRs in the mandibular condyle of mice. METHOD: Mandibular condyles of 1-, 6-, 12-, 18-, and 24-month-old C57BL/6J male mice (5 per group) were collected and histologically sectioned. Immunofluorescence for FGFs that have been reported to be relevant for chondrogenesis (FGF2, FGF8, FGF9, FGF18) as well as the activated/phosphorylated FGFRs (pFGFR1, pFGFR3) was carried out. RESULTS: FGF2 and FGF8 were strongly expressed in the cartilage and subchondral bone of 1-month-old mice, but the expression shifted mainly to the subchondral bone as mice aged. FGF18 and pFGFR3 expression was limited to the cartilage of 1-month-old mice only. Meanwhile, pFGFR1 and FGF9 were mostly limited to the cartilage with a significant increase in expression as mice aged. CONCLUSIONS: Our results indicate FGF2 and FGF8 are important growth factors for mandibular condylar cartilage growth in young mice but with limited role in the cartilage of older mice. In addition, the increased expression of pFGFR1 and FGF9 and the decreased expression of pFGFR3 and FGF18 as mice aged suggest the association of these factors with aging and osteoarthritis of the cartilage of the mandibular condyle.

Microbiota in the oral cavity of school-age children with HIV who started antiretroviral therapy at young ages in South Africa.

BACKGROUND: Infancy is an important developmental period when the microbiome is shaped. We hypothesized that earlier antiretroviral therapy (ART) initiation would attenuate HIV effects on microbiota in the mouth. METHODS: Oral swabs were collected from 477 children with HIV (CWH) and 123 children without (controls) at two sites in Johannesburg, South Africa. CWH had started ART less than 3 years of age; 63% less than 6 months of age. Most were well controlled on ART at median age 11 years when the swab was collected. Controls were age-matched and recruited from the same communities. Sequencing of V4 amplicon of 16S rRNA was done. Differences in microbial diversity and relative abundances of taxa were compared between the groups. RESULTS: CWH had lower alpha diversity than controls. Genus-level abundances of Granulicatella, Streptococcus, and Gemella were greater and Neisseria and Haemophilus less abundant among CWH than controls. Associations were stronger among boys. Associations were not attenuated with earlier ART initiation. Shifts in genus-level taxa abundances in CWH relative to controls were most marked in children on lopinavir/ritonavir regimens, with fewer shifts seen if on efavirenz ART regimens. CONCLUSION: A distinct profile of less diverse oral bacterial taxa was observed in school-aged CWH on ART compared with uninfected controls suggesting modulation of microbiota in the mouth by HIV and/or its treatments. Earlier ART initiation was not associated with microbiota profile. Proximal factors, including current ART regimen, were associated with contemporaneous profile of oral microbiota and may have masked associations with distal factors such as age at ART initiation.

Parent Attitudes regarding Orthodontists' Role as Potential Administrators of Human Papilloma Virus (HPV) Vaccines.

Objective: To assess parent attitudes regarding orthodontists' role as potential administrators of human papilloma virus (HPV) vaccines. Materials and Methods: 275 parents of adolescents, aged 11-17, who attended the orthodontic clinic at an American university for orthodontic adjustment visits and met inclusion criteria were given information about HPV and HPV vaccines. A paper questionnaire was administered to assess comfort level with orthodontists as HPV vaccinators. Demographic and other potential explanatory characteristics were collected. Descriptive, bivariate, and multivariate ordinal logistic regression analyses were performed with SPSS statistical software v25. Results: The majority of participants were between 31 and 40 years old, with 79.6% identifying as female. 54.3% of the subjects' children identified as female. Although 71.3% of participants identified as Hispanic, 55.3% of the total participants chose to respond to the questionnaire in Spanish. 66.7% of the participants reported education level as high school degree or less. Overall, 52.4% of parents responded that they would be comfortable with orthodontists administering HPV vaccines to their children. Bivariate analysis suggested a significant association (p < 0.05) of parents taking the survey in Spanish and parents' educational attainment with HPV vaccine administration comfort level. Multivariate ordinal logistic regression indicates that parents taking survey in Spanish (adjusted OR: 2.42, 95% CI: 1.24-4.72; p < .01) and parents of male children (adjusted OR: 1.66, 95% CI: 1.01-2.73; p < 047) were comfortable with orthodontists administering the HPV vaccine. Conclusions: The language of the survey influenced parents' comfort level with orthodontists as HPV vaccinators, with Spanish having a positive correlation to comfort level. Parents of male children were more comfortable with orthodontists as HPV vaccinator.

The role of inhibition of osteocyte apoptosis in mediating orthodontic tooth movement and periodontal remodeling: a pilot study.

BACKGROUND: Orthodontic tooth movement (OTM) has been shown to induce osteocyte apoptosis in alveolar bone shortly after force application. However, how osteocyte apoptosis affects orthodontic tooth movement is unknown. The goal of this study was to assess the effect of inhibition of osteocyte apoptosis on osteoclastogenesis, changes in the alveolar bone density, and the magnitude of OTM using a bisphosphonate analog (IG9402), a drug that affects osteocyte and osteoblast apoptosis but does not affect osteoclasts. MATERIAL AND METHODS: Two sets of experiments were performed. Experiment 1 was used to specifically evaluate the effect of IG9402 on osteocyte apoptosis in the alveolar bone during 24 h of OTM. For this experiment, twelve mice were divided into two groups: group 1, saline administration + OTM24-h (n=6), and group 2, IG9402 administration + OTM24-h (n=6). The contralateral unloaded sides served as the control. The goal of experiment 2 was to evaluate the role of osteocyte apoptosis on OTM magnitude and osteoclastogenesis 10 days after OTM. Twenty mice were divided into 4 groups: group 1, saline administration without OTM (n=5); group 2, IG9402 administration without OTM (n=5); group 3, saline + OTM10-day (n=6); and group 4, IG9402 + OTM10-day (n=4). For both experiments, tooth movement was achieved using Ultra Light (25g) Sentalloy Closed Coil Springs attached between the first maxillary molar and the central incisor. Linear measurements of tooth movement and alveolar bone density (BVF) were assessed by MicroCT analysis. Cell death (or apoptosis) was assessed by terminal dUTP nick-end labeling (TUNEL) assay, while osteoclast and macrophage formation were assessed by tartrate-resistant acid phosphatase (TRAP) staining and F4/80+ immunostaining. RESULTS: We found that IG9402 significantly blocked osteocyte apoptosis in alveolar bone (AB) at 24 h of OTM. At 10 days, IG9402 prevented OTM-induced loss of alveolar bone density and changed the morphology and quality of osteoclasts and macrophages, but did not significantly affect the amount of tooth movement. CONCLUSION: Our study demonstrates that osteocyte apoptosis may play a significant role in osteoclast and macrophage formation during OTM, but does not seem to play a role in the magnitude of orthodontic tooth movement.

Oral and Gut Microbial Diversity and Immune Regulation in Patients with HIV on Antiretroviral Therapy.

Despite evidence of a chronic inflammatory phenotype in people living with HIV (PLWH) on antiretroviral therapy (ART), the role of oral microbiota in chronic immune activation has not been fully explored. We aimed to determine the relationship between oral and gut microbiome diversity and chronic systemic inflammation in ART-treated PLWH with prevalent severe periodontitis, an inflammatory condition commonly associated with HIV infection. We assessed bacterial and fungal communities at oral and gastrointestinal sites in a cohort (n = 52) of primarily postmenopausal women on ART using 16S rRNA and internal transcribed spacer (ITS) sequencing and measured cellular and soluble markers of inflammation and immune dysfunction. Linear mixed-effect regression and differential abundance analyses were used to associate clinical characteristics and immunological markers with bacterial and fungal diversity and community composition. Bacterial α-diversity in plaque, saliva, and gut was associated with different immunological markers, while mycobial diversity was not associated with soluble or cellular biomarkers of immune stimulation or T cell dysfunction. Furthermore, lipopolysaccharide-positive (LPS+) bacteria previously linked to inflammatory outcomes were enriched at oral sites in patients with severe periodontitis. Fungal α-diversity was reduced in plaque from teeth with higher clinical attachment loss, a marker of periodontitis, and in saliva and plaque from patients with a history of AIDS. Our results show that both bacterial and fungal oral microbiome communities likely play a role in chronic systemic immune activation in PLWH. Thus, interventions targeting both inflammation and the microbiome, particularly in the oral cavity, may be necessary to reduce chronic immune dysregulation in patients with HIV.IMPORTANCE A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral microbiota in systemic immune activation and the relationship between oral and gut bacterial and fungal diversity have not been explored. Our study suggests a crucial role for oral bacterial and fungal communities in long-term systemic immune activation in patients on ART, expanding the current paradigm focused on gut bacteria. Our results indicate that interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-positive patients. More broadly, these findings can bolster general models of microbiome-mediated chronic systemic immune activation and aid the development of precise microbiota-targeted interventions to reverse chronic inflammation.

Structure-Function Relationships of the Temporomandibular Joint in Response to Altered Loading.

AIMS: To elucidate the effects of decreased occlusal loading (DOL), with or without reloading (RL), on the structure and bite force function of the mandibular condylar fibrocartilage in skeletally mature male mice. METHODS: At 13 weeks old, 30 wild type (WT) male mice were subjected to: (1) 6 weeks normal loading (NL); (2) 6 weeks DOL; or (3) 4 weeks DOL + 2 weeks RL. Histomorphometry, cell metabolic activity, gene expression of chondrogenic markers, and bite force tests were performed. RESULTS: DOL resulted in a significant increase in apoptosis (P < .0001) and significant decreases in fibrocartilage thickness (P < .05) and hypertrophic chondrocyte markers indian hedgehog and collagen type X (P < .05). A corresponding decrease in bite force was also observed (P < .05). RL treatment resulted in a return to values comparable to NL of chondrogenic maturation markers (P > .10), apoptosis (P > .999), and bite force (P > .90), but not in mandibular condylar fibrocartilage thickness (P > .05). CONCLUSIONS: DOL in skeletally mature mice induces mandibular condylar fibrocartilage atrophy at the hypertrophic cell layer with a corresponding decrease in bite force.

TMJ disorders: future innovations in diagnostics and therapeutics.

Because their etiologies and pathogenesis are poorly understood, temporomandibular joint (TMJ) diseases are difficult to diagnose and manage. All current approaches to treatments of TMJ diseases are largely palliative. Definitive and rational diagnoses or treatments can only be achieved through a comprehensive understanding of the etiologies, predisposing factors, and pathogenesis of TMJ diseases. While much work remains to be done in this field, novel findings in biomedicine and developments in imaging and computer technologies are beginning to provide us with a vision of future innovations in the diagnostics and therapeutics of TMJ disorders. These advances include the identification and use of local or systemic biomarkers to diagnose disease or monitor improvements in therapy; the use of imaging technologies for earlier and more sensitive diagnostics; and the use of biomedicine, biomimetics, and imaging to design and manufacture bioengineered joints. Such advances are likely to help to customize and enhance the quality of care we provide to patients with TMJ disorders.

Temporomandibular Joint Disorders in Older Adults.

OBJECTIVES: To review the literature and summarize the evidence of temporomandibualar joint (TMJ) disorders (TMDs) in older adults, focusing on clinical manifestations of TMDs in older adults, highlighting the incidence and sexual dimorphism of TMJ degeneration and the role of sex hormones in this process, and providing potential treatment options for TMD in older adults. DESIGN: Two review authors performed the literature search, study inclusion, and data extraction. PubMed, Embase, and Google scholar were searched for literature until August 2017 (Figure ). We adopted a combination of Medical Subject Headings with related free text words for the search in PubMed and optimized the search in other search engines. RESULTS: Traditionally, it was believed that TMDs predominantly affected women of childbearing age, but recent large studies in Europe and the United States have shown that the prevalence of TMD peaks after childbearing age (45-64) and then gradually decreases with age, although not much is known about the disease in older adults. CONCLUSION: Most older adults have TMJ degeneration, which affects women more than men. In most older adults, the symptoms of TMD are mild and self-limiting and can usually be treated with self management.

Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice.

Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2-macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.

Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice.

Biglycan (Bgn) and decorin (Dcn) are highly expressed in numerous tissues in the craniofacial complex. However, their expression and function in the cranial sutures are unknown. In order to study this, we first examined the expression of biglycan and decorin in the posterior frontal suture (PFS), which predictably fuses between 21 and 45 days post-natal and in the non-fusing sagittal (S) suture from wild-type (Wt) mice. Our data showed that Bgn and Dcn were expressed in both cranial sutures. We then characterized the cranial suture phenotype in Bgn deficient, Dcn deficient, Bgn/Dcn double deficient, and Wt mice. At embryonic day 18.5, alizarin red/alcian blue staining showed that the Bgn/Dcn double deficient mice had hypomineralization of the frontal and parietal craniofacial bones. Histological analysis of adult mice (45-60 days post-natal) showed that the Bgn or Dcn deficient mice had no cranial suture abnormalities and immunohistochemistry staining showed increased production of Dcn in the PFS from Bgn deficient mice. To test possible compensation of Dcn in the Bgn deficient sutures, we examined the Bgn/Dcn double deficient mice and found that they had impaired fusion of the PFS. Semi-quantitative RT-PCR analysis of RNA from 35 day-old mice revealed increased expression of Bmp-4 and Dlx-5 in the PFS compared to their non-fusing S suture in Wt tissues and decreased expression of Dlx-5 in both PF and S sutures in the Bgn/Dcn double deficient mice compared to the Wt mice. Failure of PFS fusion and hypomineralization of the calvaria in the Bgn/Dcn double deficient mice demonstrates that these extracellular matrix proteoglycans could have a role in controlling the formation and growth of the cranial vault.

Progenitor Cells of the Mandibular Condylar Cartilage.

The secondary cartilage of the mandibular condyle is unique as it undergoes endochondral ossification during growth and robustly remodels in response to changes in its mechanical loading environment. This cartilage is derived from mesenchymal progenitor cells that express markers of early osteoblast differentiation, namely alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2). Interestingly, these progenitor cells then differentiate into cartilage with appropriate mechanical loading. Our laboratory has determined that these cells can be labeled by osteoblast progenitor cell markers, including the 3.6 fragment of the rat collagen type 1. However, the role these mesenchymal progenitor cells play in adult mandibular condylar cartilage maintenance and adaptation, as well as the existence of a more potent progenitor cell population within the mandibular condylar cartilage, remain in question. Further characterization of these cells is necessary to determine their potency and regenerative capacity to elucidate their potential for regenerative therapy.

Oestrogen receptor beta mediates decreased occlusal loading induced inhibition of chondrocyte maturation in female mice.

OBJECTIVE: Temporomandibular joint (TMJ) disorders predominantly afflict women, suggesting that estrogen may play a role in the disease process. Defects in mechanical loading-induced TMJ remodelling are believed to be a major etiological factor in TMJ degenerative disease. Previously, we found that, decreased occlusal loading caused a significant decrease in early chondrocyte maturation markers (Sox9 and Col 2) in female, but not male, C57BL/6 wild type mice (1). The goal of this study was to examine the role of Estrogen Receptor (ER) beta in mediating these effects. DESIGN: 21-day-old male (n = 24) and female (n = 25) ER beta KO mice were exposed to decreased occlusal loading (soft diet administration and incisor trimming) for 4 weeks. At 49 days of age the mice were sacrificed. Proliferation, gene expression, Col 2 immunohistochemistry and micro-CT analysis were performed on the mandibular condyles. RESULTS: Decreased occlusal loading triggered similar effects in male and female ER beta KO mice; specifically, significant decreases in Col 10 expression, subchondral total volume, bone volume, and trabecular number. CONCLUSION: Decreased occlusal loading induced inhibition of chondrocyte maturation markers (Sox9 and Col 2) did not occur in female ER beta deficient mice.