Type IVb Hypersensitivity Reaction in the Novel Murine Model of Palladium-Induced Intraoral Allergic Contact Mucositis.

Palladium (Pd) is a component of several alloy types that are widely used in our environment, including several dental alloy types that cause adverse reactions such as hypersensitivity in the oral mucosa. However, the pathological mechanism of intraoral Pd allergies remains unclear because its animal model in the oral mucosa has not been established. In this study, we established a novel murine model of Pd-induced allergies in the oral mucosa, and explored the immune response of cytokine profiles and T cell diversity in terms of the T cell receptor. The Pd-induced allergy mouse was generated by two sensitizations with PdCl2, plus a lipopolysaccharide solution into the postauricular skin followed by a single Pd challenge of the buccal mucosa. Significant swelling and pathological features were histologically evident at five days after the challenge, and CD4-positive T cells producing high levels of T helper 2 type cytokines had accumulated in the allergic oral mucosa. Characterization of the T cell receptor repertoire in Palladium allergic mice indicated that Pd-specific T cell populations were limited in V and J genes but were diverse at the clonal level. Our model demonstrated that a Pd-specific T cell population with Th2 type response tendencies may be involved in the Pd-induced intraoral metal contact allergy.

Cross-Reactivity of Intraoral Allergic Contact Mucositis in the Nickel-Sensitized Ear Model of Metal Allergy.

Cross-reactivity of metal allergies can make metal allergy treatment complicated because the background of immune response in cross-reactions remains unknown. In clinical settings, cross-reactivity among several metals has been suspected. However, the precise mechanism of immune response in cross-reactivity is unclear. Two sensitizations with nickel, palladium, and chromium plus lipopolysaccharide solution into the postauricular skin were followed by a single nickel, palladium, and chromium challenge of the oral mucosa to generate the intraoral metal contact allergy mouse model. Results showed that the infiltrating T cells in nickel-sensitized, palladium- or chromium-challenged mice expressed CD8+ cells, cytotoxic granules, and inflammation-related cytokines. Thus, nickel ear sensitization can cause cross-reactive intraoral metal allergy.

Characterization of Metal-Specific T-Cells in Inflamed Oral Mucosa in a Novel Murine Model of Chromium-Induced Allergic Contact Dermatitis.

The element chromium (Cr) is a component of several types of alloys found in the environment, or utilized in dentistry, that may cause intraoral metal contact allergy. However, the pathological mechanism of intraoral Cr allergy remains unclear because there is no established animal model of Cr allergy in the oral mucosa. In this study, we established a novel murine model of Cr-induced intraoral metal contact allergy and elucidated the immune response in terms of cytokine profiles and T-cell receptor repertoire. Two sensitizations with Cr plus lipopolysaccharide solution into the postauricular skin were followed by a single Cr challenge of the oral mucosa to generate the intraoral metal contact allergy model. Histological examination revealed that CD3+ T-cells had infiltrated the allergic oral mucosa one day after exposure to the allergen. The increase in T-cell markers and cytokines in allergic oral mucosa was also confirmed via quantitative PCR analysis. We detected Cr-specific T-cells bearing TRAV12D-1-TRAJ22 and natural killer (NK) T-cells in the oral mucosa and lymph nodes. Our model demonstrated that Cr-specific T-cells and potent NKT-cell activation may be involved in the immune responses of Cr-induced intraoral metal contact allergy.

Constructing an Emotion Estimation Model Based on EEG/HRV Indexes Using Feature Extraction and Feature Selection Algorithms.

In human emotion estimation using an electroencephalogram (EEG) and heart rate variability (HRV), there are two main issues as far as we know. The first is that measurement devices for physiological signals are expensive and not easy to wear. The second is that unnecessary physiological indexes have not been removed, which is likely to decrease the accuracy of machine learning models. In this study, we used single-channel EEG sensor and photoplethysmography (PPG) sensor, which are inexpensive and easy to wear. We collected data from 25 participants (18 males and 7 females) and used a deep learning algorithm to construct an emotion classification model based on Arousal-Valence space using several feature combinations obtained from physiological indexes selected based on our criteria including our proposed feature selection methods. We then performed accuracy verification, applying a stratified 10-fold cross-validation method to the constructed models. The results showed that model accuracies are as high as 90% to 99% by applying the features selection methods we proposed, which suggests that a small number of physiological indexes, even from inexpensive sensors, can be used to construct an accurate emotion classification model if an appropriate feature selection method is applied. Our research results contribute to the improvement of an emotion classification model with a higher accuracy, less cost, and that is less time consuming, which has the potential to be further applied to various areas of applications.

Automatic whole brain vascular territory mapping.

Cerebral vascular territories are related to the clinical progression and outcome of ischemic stroke. The vascular territory map (VTM) helps to understand stroke pathophysiology and potentially the clinical prognosis. A VTM can be generated from the bolus arrival time map. However, previous methods require initial seed points to be chosen manually, and the region inferior to the circle of Willis is not included. In this paper, we propose a method to automatically generate a map of the whole cerebral vascular territory from CT perfusion imaging. We applied the proposed method to 19 cases of ischemic stroke to generate VTM for each case.Clinical Relevance- The proposed map may improve the interpretation of the physiological status of collateral flow for ischemic stroke, and aid in treatment decision making.

Cross-Reactivity of Palladium in a Murine Model of Metal-Induced Allergic Contact Dermatitis.

Metal allergy is usually diagnosed by patch testing, however, the results do not necessarily reflect the clinical symptoms because of cross-reactivity between different metals. In this study, we established the novel mouse model of cross-reactive metal allergy, and aimed to elucidate the immune response in terms of T-cell receptor repertoire. This model was classified into two groups: the sensitization to nickel and challenge with palladium group, and the sensitization to chromium and challenge with palladium group. This model developed spongiotic edema with intra- and peri-epithelial infiltration of CD4+ T cells in the inflamed skin that resembles human contact dermatitis. Using T cell receptor analysis, we detected a high proportion of T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 in the Ni- and Cr-sensitized Pd-challenged mice. Furthermore, mucosal-associated invariant T cells and invariant natural killer T cells were also detected. Our results indicated that T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 induced the development of palladium-cross reactive allergy, and that mucosal-associated invariant T and invariant natural killer T cells were also involved in the cross-reactivity between different metals.

Characterization of T cell receptors in a novel murine model of nickel-induced intraoral metal contact allergy.

Nickel is a component of several alloy types that are widely used in our environment, including several dental alloy types that cause intraoral metal contact allergy. However, metal-specific immune responses in the oral mucosa have not been elucidated because a suitable animal model has not been established. In this study, we established a novel murine model of nickel-induced intraoral metal contact allergy and aimed to elucidate the immune response in terms of T-cell receptor repertoire and cytokine profiles in inflamed oral mucosa. The intraoral metal contact allergy model was induced by two sensitizations of nickel plus lipopolysaccharide solution into the postauricular skin followed by a single nickel challenge of the buccal mucosa. Cytokine expression profiles and T-cell phenotypes were determined by quantitative polymerase chain reaction. T cells accumulated in the cervical lymph nodes and inflamed oral mucosa were characterized by analyzing their T-cell receptor α- and ß-chain repertoires, and the nucleotide sequences of complementary determining region 3. Significant swelling and pathological features were histologically evident at 1 day after challenge in mice with nickel allergy. At 1 day after the challenge, CD8-positive T cells producing high levels of T helper 1 type cytokines had accumulated in the allergic oral mucosa. At 7 days after the challenge, excessive nickel allergy in the oral mucosa was suppressed by regulatory T cells. Characterization of the T-cell receptor repertoire in nickel allergic mice revealed the presence of natural killer T cells and T cells bearing Trav6-6-Traj57 at 1 day after the challenge. Our murine model of nickel-induced intraoral metal contact allergy showed that natural killer T cells and T cells bearing Trav6-6-Traj57 might be involved in the immune responses of nickel-induced intraoral metal contact allergy.

Oral Methotrexate-related Lymphoproliferative Disease Presenting with Severe Osteonecrosis of the Jaw: A Case Report and Literature Review.

Long-term methotrexate (MTX) treatment can cause MTX-related lymphoproliferative disorder (MTX-LPD). We experienced a case of MTX-LPD that was associated with severe osteonecrosis of the jaw mimicking medication-related osteonecrosis of the jaw. The patient was an 81-year-old woman with rheumatoid arthritis (RA) who was treated with MTX and bisphosphonate. After 7 years, she was referred to our department for the assessment of giant ulcer and exposure of the alveolar bone of the left maxilla. Histopathological and immunological analyses confirmed a diagnosis of MTX-LPD. At seven months after the cessation of MTX treatment, the ulcerative and necrotic lesions had markedly decreased in size. A 1-year follow-up examination showed no evidence of recurrence and good RA control.

Tumor-suppressive roles of ΔNp63ß-miR-205 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma via targeting ZEB1 and ZEB2.

We previously revealed that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63ß, a splicing variant of ΔNp63, in oral squamous cell carcinoma (OSCC). Recent studies have highlighted the involvement of microRNA (miRNA) in EMT of cancer cells, though the mechanism remains unclear. To identify miRNAs responsible for ΔNp63ß-mediated EMT, miRNA microarray analyses were performed by ΔNp63ß-overexpression in OSCC cells; SQUU-B, which lacks ΔNp63 expression and displays EMT phenotypes. miRNAs microarray analyses revealed miR-205 was the most up-regulated following ΔNp63ß-overexpression. In OSCC cells, miR-205 expression was positively associated with ΔNp63 and negatively with zinc-finger E-box binding homeobox (ZEB) 1 and ZEB2, potential targets of miR-205. miR-205 overexpression by miR-205 mimic transfection into SQUU-B cells led to decreasing ZEB1, ZEB2, and mesenchymal markers, increasing epithelial markers, and reducing cell motilities, suggesting inhibition of EMT phenotype. Interestingly, the results opposite to this phenomenon were obtained by transfection of miR-205 inhibitor into OSCC cells, which express ΔNp63 and miR-205. Furthermore, target protector analyses revealed direct regulation by miR-205 of ZEB1 and ZEB2 expression. These results showed tumor-suppressive roles of ΔNp63ß and miR-205 by inhibiting EMT thorough modulating ZEB1 and ZEB2 expression in OSCC.

Differential roles of kallikrein-related peptidase 6 in malignant transformation and ΔNp63ß-mediated epithelial-mesenchymal transition of oral squamous cell carcinoma.

We previously reported that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63ß in oral squamous cell carcinoma (OSCC). In this study, DNA microarray analyses were performed using ΔNp63ß-overexpressing OSCC cells to identify genes associated with ΔNp63ß-mediated EMT. Thereby, we focused on kallikrein-related peptidase (KLK) 6, most up-regulated following ΔNp63ß-overexpression, that activates protease-activated receptors (PARs). In RT-PCR analyses, ΔNp63 was positively associated with KLK6 and PAR2 and negatively with PAR1 in OSCC cells. By ΔNp63 knockdown, KLK6 and PAR2 expression was decreased and PAR1 was increased. Furthermore, KLK6 knockdown led to enhancing migration and invasion, and inhibiting proliferation, suggesting EMT-phenotypes. Although, in the KLK6 or PAR2 knockdown cells, phosphorylation of ERK was reduced, it was restored in the KLK6 knockdown OSCC cells treated with recombinant KLK6 proteins. Immunohistochemistry showed ΔNp63, KLK6, and PAR2 were more strongly expressed in the epithelial dysplasia and central region of OSCC than normal oral epithelium, whereas PAR1 expression was undetectable. Interestingly, at the invasive front of OSCC, ΔNp63, KLK6, and PAR2 were reduced, but PAR1 was elevated. In addition, the OSCC patients with decreasing KLK6 expression at the invasive front had more unfavourable prognosis. These results suggested differential roles of KLK6 in malignant transformation and EMT; high ΔNp63ß expression up-regulates KLK6-PAR2 and down-regulates PAR1, inducing malignant transformation in oral epithelium with stimulating proliferation through ERK signal activation. Moreover, KLK6-PAR2 expression is down-regulated and PAR1 is up-regulated when ΔNp63ß expression is decreased, leading to EMT with enhancing migration and invasion through ERK signal reduction at the invasive front.

Cytokeratin 17 mRNA as a prognostic marker of oral squamous cell carcinoma.

Despite diagnostic and therapeutic advances, the 5-year survival rate of oral squamous cell carcinoma (OSCC) remains between 70-80% due to recurrences and secondary metastases to cervical lymph nodes. It is difficult to find these recurrences and metastases postoperatively, thus, careful follow-up is recommended. Cytokeratins (CKs) are intermediate filaments of the cytoskeleton and candidate prognostic biomarkers for OSCC, as they are overexpressed in OSCC compared with normal mucosa. The aim of the present study was to determine the relative levels of occurrence of 3 CK mRNA (CK17, CK19, CK20) transcripts in peripheral blood mononuclear cells (PBMC) using reverse transcription-quantitative polymerase chain reaction. The study comprised pre- and post-operative PBMC samples from 19 OSCC patients. In the good-prognosis group, 10 of 13 patients demonstrated reduced CK17 mRNA expression post-operatively, compared with pre-operative samples, conversely, only 3 of 6 patients in the poor-prognosis group had reduced post-operative CK17 mRNA expression. This difference was statistically significant (P<0.01). The disease-free survival rate of the group with reduced post-operative CK17 mRNA expression was significantly increased compared with the elevated CK17 mRNA group (P<0.01); however, the overall survival rates of the two groups were not significantly different. Neither CK19 mRNA nor CK20 mRNA were significantly expressed in the PBMC of OSCC patients. Overall, CK17 mRNA expression may be a useful prognostic biomarker for OSCC.

Fexofenadine Suppresses Delayed-Type Hypersensitivity in the Murine Model of Palladium Allergy.

Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical setting, glucocorticoids and antihistamine drugs are commonly used for treatment of contact dermatitis. However, the precise mechanism of immune suppression in palladium allergy remains unknown. We investigated inhibition of the immune response in palladium allergic mice by administration of prednisolone as a glucocorticoid and fexofenadine hydrochloride as an antihistamine. Compared with glucocorticoids, fexofenadine hydrochloride significantly suppressed the number of T cells by interfering with the development of antigen-presenting cells from the sensitization phase. Our results suggest that antihistamine has a beneficial effect on the treatment of palladium allergy compared to glucocorticoids.

Critical roles of Wnt5a-Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloproteinase-2 via ΔNp63ß-mediated epithelial-mesenchymal transition.

OBJECTIVES: We previously showed that ΔNp63ß, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63ß affects cell motility. As the results, Wnt5a was significantly down-regulated by ΔNp63ß overexpression in tongue SCC cell line (SQUU-B) with EMT phenotype. MATERIALS AND METHODS: Seven OSCC cell lines were used. Expression of ΔNp63, Wnt5a, its receptor Ror2, and matrix metalloproteinases (MMPs) were analyzed by RT-PCR, real-time PCR, and western blotting, and gelatin zymography. Furthermore, we examined the effects of siRNA for Wnt5a or Ror2 and recombinant human Wnt5a (rhWnt5a) on motility of tongue SCC cells. Biopsy specimens from tongue SCC patients were used for immunohistochemical staining of Wnt5a and Ror2. RESULTS: Wnt5a and Ror2 were expressed only in SQUU-B cells without ΔNp63 expression, and negatively associated with ΔNp63 expression in other cells. ΔNp63ß overexpression in SQUU-B cells decreased Wnt5a and Ror2 expression. By Wnt5a or Ror2 knockdown, cell motility was remarkably inhibited, but EMT markers expression was unaffected. MMP-2 expression and the activities inversely correlated with ΔNp63 expression, and were inhibited by Wnt5a or Ror2 knockdown. Cell motility and MMP-2 activities were recovered by adding rhWnt5a in the cells with Wnt5a knockdown, but not in those with Ror2 knockdown. Moreover, immunohistochemical analyses in tongue SCC specimens found that high expression of Wnt5a or Ror2 was associated with poorer prognosis. CONCLUSION: Wnt5a-Ror2 signaling enhanced tongue SCC cell aggressiveness and promoted production of MMP-2 following ΔNp63ß-mediated EMT.

Overexpression of ErbB4 is an independent marker for lymph node metastasis in Japanese patients with oral squamous cell carcinoma.

OBJECTIVE: Overexpression of the epidermal growth factor receptor (EGFR) family is common in oral squamous cell carcinoma (OSCC). Therefore, we analyzed the expression profiles of the four EGFR family members (ErbB1, ErbB2, ErbB3, and ErbB4) in OSCC of Japanese patients. STUDY DESIGN: Sixty-eight primary tumors and 18 normal oral mucosal tissue specimens were evaluated in this study. We analyzed EGFR family members using quantitative polymerase chain reaction and immunohistochemistry, as well as their relationships with clinical factors. RESULTS: The expression level of ErbB1 messenger RNA (mRNA) was markedly increased in OSCC. By comparing the gene expression levels of EGFR family members in OSCC tissues that had lymph node metastasis with those in the absence of lymph node metastasis, we found that ErbB4 mRNA expression was increased significantly. There was also a significant correlation between the mRNA expression level of ErbB4 and those of ErbB2 and ErbB3 in cases with lymph node metastasis. Moreover, we confirmed protein expression of ErbB4 in the cytoplasm and membrane of tumor cells, which was stronger in cases with lymph node metastasis. CONCLUSIONS: ErbB4 is an independent marker for lymph node metastasis in OSCC.

Tongue squamous cell carcinoma producing both parathyroid hormone-related protein and granulocyte colony-stimulating factor: a case report and literature review.

BACKGROUND: Paraneoplastic syndrome generally results from tumor-derived hormones or peptides that cause metabolic derangements. Common metabolic conditions include hyponatremia, hypercalcemia, hypoglycemia, and Cushing's syndrome. Herein, we report a very rare case of tongue carcinoma presenting with leukocytosis and hypercalcemia. CASE PRESENTATION: A 57-year-old man was admitted to our hospital with tongue squamous cell carcinoma (cT4aN0M0, stage IV). He underwent radical resection following preoperative chemoradiotherapy, but locoregional recurrence was detected 2 months after surgery. He presented with marked leukocytosis and hypercalcemia with elevated serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP). He was therefore managed with intravenous fluids, furosemide, prednisolone, elcatonin, and pamidronate. However, the patient died 1 month later of carcinomatous pleuritis following distant metastasis to the lung. Immunohistochemical analyses of the resected specimens revealed positive staining for PTHrP and G-CSF in the cancer cells. CONCLUSIONS: In this case, it was considered that tumor-derived G-CSF and PTHrP caused leukocytosis and hypercalcemia.

Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma.

The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80-120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2-6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment.

Surface vacuolar ATPase in ameloblastoma contributes to tumor invasion of the jaw bone.

Ameloblastoma is the most common benign odontogenic tumor in Japan. It is believed that it expands in the jaw bone through peritumoral activation of osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL) released from the ameloblastoma, as in bone metastases of cancer cells. However, the clinical features of ameloblastoma, including its growth rate and patterns of invasion, are quite different from those of bone metastasis of cancer cells, suggesting that different underlying mechanisms are involved. Therefore, in the present study, we examined the possible mechanisms underlying the invasive expansion of ameloblastoma in the jaw bone. Expression levels of RANKL assessed by western blotting were markedly lower in ameloblastoma (AM-1) cells than in highly metastatic oral squamous cell carcinoma (HSC-3) cells. Experiments coculturing mouse macrophages (RAW264.7) with AM-1 demonstrated low osteoclastogenic activity, as assessed by tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cell formation, probably because of low release of RANKL, whereas cocultures of RAW264.7 with HSC-3 cells exhibited very high osteoclastogenic activity. Thus, RANKL release from AM-1 appeared to be too low to generate osteoclasts. However, AM-1 cultured directly on calcium phosphate-coated plates formed resorption pits, and this was inhibited by application of bafilomycin A1. Furthermore, vacuolar-type H+-ATPase (V-ATPase) and H+/Cl- exchange transporter 7 (CLC-7) were detected on the surface of AM-1 cells by plasma membrane biotinylation and immunofluorescence analysis. Immunohistochemical analysis of clinical samples of ameloblastoma also showed plasma membrane-localized V-ATPase and CLC-7 in the epithelium of plexiform, follicular and basal cell types. The demineralization activity of AM-1 was only 1.7% of osteoclasts demineralization activity, and the growth rate was 20% of human normal skin keratinocytes and HSC-3 cells. These results suggest that the slow expansion of several typical types of ameloblastomas in jaw bone is attributable to its slow growth and low demineralization ability.

Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis.

Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion-induced allergic contact dermatitis.

Spontaneously developed osteoarthritis in the temporomandibular joint in STR/ort mice.

Temporomandibular joint (TMJ) osteoarthritis is typically a slowly progressive asymmetric disease. Little is known regarding the natural destruction of TMJ articular tissues. The aim of the present study was to investigate morphological changes in the TMJ of STR/ort mice, known to be the model for spontaneous osteoarthritis in the knee joint, and to evaluate STR/ort mice as a suitable animal model for TMJ osteoarthritis. TMJs from 32 STR/ort mice euthanized at 30, 40, 50 or 60 weeks of age, and from 6 CBA mice euthanized at 30, 40 or 60 weeks of age were examined. Toluidine blue and tartrate-resistant acid phosphatase staining were used to assess histological changes in the articular cartilage. Morphological changes in the articular cartilage of the TMJ were evaluated using microcomputed tomography. At the age of 40-50 weeks, 17 (68%) of the 25 STR/ort mice had loss of articular cartilage on histology, with cavitation and erosion of the exposed bone and gradual changes in condylar shape. Furthermore, osteoarthritic morphological changes, and structural alterations were observed by microcomputed tomography. The STR/ort mouse strain appears to develop spontaneous osteoarthritis-like lesions in the TMJ with age, and would be a useful model to study the pathogenesis of TMJ osteoarthritis.