Prevalence and associated factors of health anxiety in patients with temporomandibular disorders.

OBJECTIVES: To investigate the prevalence and associated factors of health anxiety (HA) in patients with Temporomandibular Disorders (TMDs) using the 8-item Whiteley Index (WI-8) scale. MATERIALS AND METHODS: Three hundred and twenty-nine TMDs patients completed the Visual Analog Scale (VAS), WI-8, Jaw Functional Limitation Scale-8 (JFLS-8), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) scales. Clinical examinations were conducted following the Diagnostic Criteria for TMDs Axis I. RESULTS: The prevalence of HA among TMDs patients was 18.54%. Patients with HA had higher scores of VAS-current (p = 0.026), VAS-maximum (p = 0.024), VAS-average (p = 0.030), JFLS-8 (p < 0.001), GAD-7 (p < 0.001) and PHQ-9 (p < 0.001), lower maximum mouth opening (p = 0.016), lower proportion of structure-related TMDs (p = 0.028), and higher proportion of pain-related TMDs (p < 0.001) compared to those without HA. The correlation coefficient was 0.61 (p < 0.001) between WI-8 and GAD-7 and 0.64 (p < 0.001) between WI-8 and PHQ-9. CONCLUSION: Approximately one-fifth of patients with TMDs experienced HA. HA was associated with pain perception, functional limitations, depressive, and anxiety symptoms in individuals with TMDs. HA may contribute to heightened subjective pain experiences rather than structural changes in the TMJ.

Relationship Between Temporomandibular Joint Effusion, Pain, and Jaw Function Limitation: A 2D and 3D Comparative Study.

Purpose: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation. Patients and Methods: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p<0.05 was considered statistically significant. Results: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008). Conclusion: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation.

Agaricus blazei Murrill Polysaccharide Attenuates Periodontitis via H2 S/NRF2 Axis-Boosted Appropriate Level of Autophagy in PDLCs.

SCOPE: Periodontitis is one of the most prevalent chronic inflammatory diseases with impaired autophagy. Agaricus blazei Murrill polysaccharide (ABMP) shows beneficial effects in various inflammatory diseases. However, whether ABMP is involved in autophagy regulation and periodontitis attenuation remains to be elucidated. METHODS AND RESULTS: This study firstly shows the dynamic changes in inflammatory and autophagy levels in silk ligature periodontitis model. Then the positive regulation effect of autophagy on inflammation and its vital role in ABMP inhibiting PDLCs inflammatory response are testified in LPS-treated PDLCs. Secondly, the Micro-CT, quantitative RT-PCR, Western Blot, TRAP, and immunofluorescence staining analysis are performed to assess the effects of ABMP on periodontitis and autophagy. The data show the augmented autophagy and alleviated gingival recession, inflammatory cell infiltration, alveolar bone resorption, and reduced osteoclasts in periodontitis by ABMP treatment. Further experiments using chemical inhibitors demonstrate the vital role of H2 S/NRF2 axis in ABMP-induced appropriate level of autophagy augmentation against periodontitis. CONCLUSIONS: Collectively, the findings not only reveal the unrecognized capacity and mechanism of ABMP as an effective and potential dietary intake against periodontitis, but also suggest the possibility for ABMP to be used in the treatment of other autophagy-related diseases.

Low income is associated with impaired jaw function via anxiety and depression in patients with temporomandibular disorders.

OBJECTIVE: The association between jaw function and income in patients with temporomandibular disorders (TMDs) remain unclear. The aim of this study was to explore this association and its relationship with anxiety and depression. SUBJECTS AND METHODS: A total of 451 TMD patients, including 361 males and 90 females, participated in this study. The sociodemographic information of patients and their questionnaires including the Generalised Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire 9-item (PHQ-9), and Jaw Functional Limitation Scale-8 (JFLS-8) were collected. Patients were divided into the high-income and low-income groups based on a household per capita income of 6000 RMB per month. Multiple regression and mediation analysis were used to explore the association between variables. The bootstrap method was applied to estimate confidence intervals (CIs). RESULTS: Higher JFLS-8 scores were significantly correlated with higher GAD-7 scores (r = 0.361, p < .001), PHQ-9 scores (r = 0.339, p < .001). Females and patients with low income had statistically higher JFLS-8 scores (p < .01, p < .001). Mediation analysis with 10 000 bootstrap simulations revealed a significant direct association between JFLS-8 scores and income (-2.920, 95% CI [-4.757, -1.044], p = .002). A significant indirect association of JFLS-8 scores with income via GAD-7 scores and PHQ-9 scores was also observed (-0.889, 95% CI [-1.728, -0.164], p = .025), accounting for 23.3% of the total association. CONCLUSIONS: Low income is associated with impaired jaw function via anxiety and depression in patients with TMD. Clinicians may need to pay more attention to the psychological status of low-income TMD patients in clinical practice.

Polydopamine-Mediated Immunomodulatory Patch for Diabetic Periodontal Tissue Regeneration Assisted by Metformin-ZIF System.

An essential challenge in diabetic periodontal regeneration is achieving the transition from a hyperglycemic inflammatory microenvironment to a regenerative one. Here, we describe a polydopamine (PDA)-mediated ultralong silk microfiber (PDA-mSF) and metformin (Met)-loaded zeolitic imidazolate framework (ZIF) incorporated into a silk fibroin/gelatin (SG) patch to promote periodontal soft and hard tissue regeneration by regulating the immunomodulatory microenvironment. The PDA-mSF endows the patch with a reactive oxygen species (ROS)-scavenging ability and anti-inflammatory activity, reducing the inflammatory response by suppressing M1 macrophage polarization. Moreover, PDA improves periodontal ligament reconstruction via its cell affinity. Sustained release of Met from the Met-ZIF system confers the patch with antiaging and immunomodulatory abilities by activating M2 macrophage polarization to secrete osteogenesis-related cytokines, while release of Zn2+ also promotes bone regeneration. Consequently, the Met-ZIF system creates a favorable microenvironment for periodontal tissue regeneration. These features synergistically accelerate diabetic periodontal bone and ligament regeneration. Thus, our findings offer a potential therapeutic strategy for hard and soft tissue regeneration in diabetic periodontitis.

Knowledge and Attitudes regarding Temporomandibular Disorders among Postgraduate Dental Students and Practicing Dentists in Western China: A Questionnaire-Based Observational Investigation.

Background: It is necessary for dental students and dentists to apply their temporomandibular disorders (TMDs)-related knowledge to clinical practice. The current study aimed to evaluate the knowledge and awareness of postgraduate dental students and practicing dentists regarding etiology, diagnosis, and treatment of TMD in western China and thus provide suggestions on TMD curricula design to get postgraduate students and dentists better prepared for TMD diagnosis and treatment. Methods: This observational and descriptive cross-sectional study was conducted among postgraduate students and practicing dentists in western China. Twenty-five reorganized knowledge questions in four domains were selected from the published literature and were evaluated with answer options from "strongly agree" to "strongly disagree," and "I don't know." "Consensus" is defined as more than 50% of respondents in a group agree or disagree with a statement. Chi-square tests were performed for comparisons between the two groups. Results: A total of 132 postgraduate dental students and 123 dentists completed the questionnaire. Around 75% of postgraduate students and 85% of dentists claimed that they have never participated in systematic training in TMD. Nine statements in etiology, diagnosis, treatment, and prognosis of TMD had different consensus between the two groups. And the dentist group tended to agree more with 12 statements in the questionnaire. Conclusions: The majority of Chinese dentists and dental students have not taken any TMD courses and possess limited knowledge of TMD. Curriculum reform for predoctoral education, postgraduate education, and continuing education is needed to augment knowledge and skills for TMD diagnosis and treatment.

Age and Gender, but Not Pain are Associated with Pressure Pain Thresholds in Patients with Temporomandibular Disorders: A Cross-Sectional Study.

Purpose: This study aims to explore the association of pressure pain thresholds (PPTs) with age, gender, and pain in patients with temporomandibular disorders (TMD). Patients and Methods: A total of 301 TMD patients (248 female and 53 male) were recruited and classified into the high and low age groups according to their median age of 26 years. Patients' demographics, pain-related variables, TMD-related variables, and PPTs of both left and right temporomandibular joints (TMJs), masseter, and temporalis were collected. Results: Pain duration and visual analog scale of pain (VAS) showed no significant correlations with PPTs (P>0.05). Multiple linear regression analysis revealed a significant positive association of PPTs of all six sites with males (ß=0.41-0.72 kg·cm-2, 95% CI (0.19-0.38, 0.74-0.99), P<0.001), as well as with the high age group [ß=0.28-0.36 kg·cm-2, 95% CI (0.07-0.20, 0.47-0.53), P<0.020]. Furthermore, PPTs of the left TMJ showed a significant negative association with left pain-related TMD (PT) [ß=-0.21 kg·cm-2, 95% CI (-0.38, -0.04), P=0.026], but PPTs of the remaining sites did not show a significant association with PT (P>0.05). Stratified analysis showed that PPTs in females were associated with the high age group [ß=0.25-0.37 kg·cm-2, 95% CI (0.04-0.20, 0.45-0.56), P<0.020] and that PPT of the left TMJ was associated with left PT [ß=-0.21 kg·cm-2, 95% CI (-0.39, -0.03), P=0.043]. The remaining PPTs did not show a significant association with PT (P>0.05). In males, PPTs did not show significant correlations with age, PT and VAS (P>0.05). Conclusion: PPTs in the orofacial region are associated with gender and age in TMD patients. Pain duration and intensity show no significant correlations with PPTs in TMD patients. Researchers and dentists should take age and gender into account when using PPTs as auxiliary diagnostic indicators for PT.

Enlarged occipital spur and craniofacial morphology: a cephalometric analysis.

OBJECTIVE: This cross-sectional study aimed to investigate the association between the occipital spur length and craniofacial morphology in individuals with occipital spur (OS). METHODS: The study included cephalometric images from 451 individuals (196 females, 255 males, age range was 9-84 years). The spur length and craniofacial characteristics were evaluated using cephalograms. Based on spur length, subjects were divided into two groups: the OS group (N = 209) and the enlarged occipital spur (EOS) group (N = 242). Descriptive statistics, Independent T-test, Mann-Whitney U test, chi-square test, Kruskal-Wallis test, and age- and sex-based stratified analyses were performed. The level of significance was set at p < 0.05. RESULTS: Males had significantly larger spur length than females. Spur length was shorter in individuals under 18 than the groups over 18. After adjusting for gender and age, ramus height, mandibular body length, effective length of maxilla, effective length of mandible, anterior cranial base length, posterior cranial base length, anterior facial height, posterior facial height, facial height index, and lower anterior facial height had statistically significant differences between OS group and EOS group. CONCLUSIONS: Males exhibit greater spur length than females. Patients under 18 had a shorter spur length than adults. Linear craniofacial measurements were found to be greater in subjects with EOS than the individuals with OS. The craniofacial growth and development of an individual might be associated with EOS. The causal relationship between EOS and craniofacial development requires further longitudinal studies.

Risk estimation of degenerative joint disease in temporomandibular disorder patients with different types of sagittal and coronal disc displacements: MRI and CBCT analysis.

BACKGROUND: Degenerative joint disease (DJD) can be associated with disc displacement (DD) in temporomandibular disorder (TMD) patients. However, the relationship between different types of DDs and DJD remains unclear. OBJECTIVES: To investigate the odds ratios of different types of sagittal and coronal DDs confirmed by magnetic resonance imaging (MRI) and DJD confirmed by cone-beam computed tomography (CBCT) in TMD patients. METHODS: Radiographic data from 69 males and 232 females were collected for analysis. CBCT was used to diagnose DJD, with criteria including erosion, osteophytes, generalised sclerosis and cysts in the joint. Eight types of DDs were evaluated by sagittal and coronal MRIs: NA, no abnormality; SW, sideways; ADDR, anterior with reduction; ADDR+SW; ADDNR, anterior without reduction; ADDNR + SW; single SW; PDD, posterior; PDD + SW. The odds ratios of DJD in joints with different types of DDs were determined after joint correlation, age and gender adjustment. RESULTS: Compared with NA, the odds ratio of DJD in ADDR was 2.397 (95% CI [confidence interval]: 1.070-5.368), ADDR + SW was 4.808 (95% CI: 1.709-3.528), ADDNR was 29.982 (95% CI: 15.512-57.950) and ADDNR + SW was 25.974 (95% CI: 12.743-52.945). Erosion was significantly increased in ADDR, ADDR + SW, ADDNR and ADDNR + SW; osteophytes were significantly increased in ADDR + SW, ADDNR and ADDNR + SW; and generalised sclerosis and cysts were significantly increased in ADDNR and ADDNR + SW. There were no significant associations between single SW, PDD, PDD + SW and the DJD. CONCLUSIONS: ADDR, ADDR+SW, ADDNR and ADDNR+SW were associated with DJD. ADDNR had a significantly higher prevalence of DJD than ADDR. There were no significant relationships between single SW, PDD, PDD + SW and the DJD.

A new frontier in temporomandibular joint osteoarthritis treatment: Exosome-based therapeutic strategy.

Temporomandibular joint osteoarthritis (TMJOA) is a debilitating degenerative disease with high incidence, deteriorating quality of patient life. Currently, due to ambiguous etiology, the traditional clinical strategies of TMJOA emphasize on symptomatic treatments such as pain relief and inflammation alleviation, which are unable to halt or reverse the destruction of cartilage or subchondral bone. A number of studies have suggested the potential application prospect of mesenchymal stem cells (MSCs)-based therapy in TMJOA and other cartilage injury. Worthy of note, exosomes are increasingly being considered the principal efficacious agent of MSC secretions for TMJOA management. The extensive study of exosomes (derived from MSCs, synoviocytes, chondrocytes or adipose tissue et al.) on arthritis recently, has indicated exosomes and their specific miRNA components to be potential therapeutic agents for TMJOA. In this review, we aim to systematically summarize therapeutic properties and underlying mechanisms of MSCs and exosomes from different sources in TMJOA, also analyze and discuss the approaches to optimization, challenges, and prospects of exosome-based therapeutic strategy.

Immune senescence and periodontitis: From mechanism to therapy.

Periodontitis is one of the most prevalent infectious inflammatory diseases, characterized by irreversible destruction of the supporting tissues of teeth, which is correlated with a greater risk of multiple systemic diseases, thus regarded as a major health concern. Dysregulation between periodontal microbial community and host immunity is considered to be the leading cause of periodontitis. Comprehensive studies have unveiled the double-edged role of immune response in the development of periodontitis. Immune senescence, which is described as age-related alterations in immune system, including a diminished immune response to endogenous and exogenous stimuli, a decline in the efficiency of immune protection, and even failure in immunity build-up after vaccination, leads to the increased susceptibility to infection. Recently, the intimate relationship between immune senescence and periodontitis has come into focus, especially in the aging population. In this review, both periodontal immunity and immune senescence will be fully introduced, especially their roles in the pathology and progression of periodontitis. Furthermore, novel immunotherapies targeting immune senescence are presented to provide potential targets for research and clinical intervention in the future.

SM22α-lineage niche cells regulate intramembranous bone regeneration via PDGFRß-triggered hydrogen sulfide production.

Bone stromal cells are critical for bone homeostasis and regeneration. Growing evidence suggests that non-stem bone niche cells support bone homeostasis and regeneration via paracrine mechanisms, which remain to be elucidated. Here, we show that physiologically quiescent SM22α-lineage stromal cells expand after bone injury to regulate diverse processes of intramembranous bone regeneration. The majority of SM22α-lineage cells neither act as stem cells in vivo nor show their expression patterns. Dysfunction of SM22α-lineage niche cells induced by loss of platelet-derived growth factor receptor ß (PDGFRß) impairs bone repair. We further show that PDGFRß-triggered hydrogen sulfide (H2S) generation in SM22α-lineage niche cells facilitates osteogenesis and angiogenesis and suppresses overactive osteoclastogenesis. Collectively, these data demonstrate that non-stem SM22α-lineage niche cells support the niche for bone regeneration with a PDGFRß/H2S-dependent regulatory mechanism. Our findings provide further insight into non-stem bone stromal niche cell populations and niche-regulation strategy for bone repair.

Customized maxillary incisor position relative to dentoskeletal and soft tissue patterns in Chinese women: A retrospective study.

Objective: To provide reliable prediction models based on dentoskeletal and soft tissue variables for customizing maxillary incisor positions and to optimize digitalized orthodontic treatment planning. Methods: This study included 244 Chinese women (age, 18-40 years old) with esthetic profiles after orthodontic treatment with fixed appliances (133 in group I: 1° ≤ The angle between the nasion [N]-A point [A] plane and the N-B point [B] plane [ANB] ≤ 4°; 111 in group II: 4° < ANB ≤ 7°). Dental, skeletal, and soft tissue measurements were performed on lateral cephalograms of the participants. Correlation and multiple linear regression analyses were used to determine the influence of dentoskeletal and soft tissue variables on maxillary incisor position. Results: The ideal anteroposterior position of the maxillary incisor varied between sagittal skeletal patterns. The position of the maxillary incisor correlated with the sagittal discrepancy between the maxilla and the mandible (ANB), protrusion of the midface, nasal tip projection, development of the chin, and inclination of both the maxillary and mandibular incisors. Distance from the maxillary central incisor to nasion-pogonion plane predicted using multiple linear regression analysis was accurate and could be a practical measurement in orthodontic treatment planning. Conclusions: Instead of using an average value or norm, orthodontists should customize a patient's ideal maxillary incisor position using dentoskeletal and soft tissue evaluations.

Gli1+ Mesenchymal Stem Cells in Bone and Teeth.

Mesenchymal stem cells (MSCs) are remarkable and noteworthy. Identification of markers for MSCs enables the study of their niche in vivo. It has been identified that glioma-associated oncogene 1 positive (Gli1+) cells are mesenchymal stem cells supporting homeostasis and injury repair, especially in the skeletal system and teeth. This review outlines the role of Gli1+ cells as MSC subpopulation in both bones and teeth, suggesting the prospects of Gli1 an + cells in stem cell- based tissue engineering.

Comparison and applicability of three induction methods of temporomandibular joint osteoarthritis in murine models.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) causes severe symptoms such as chewing difficulties, acute pain and even maxillofacial deformity. However, there is hardly any effective disease-curing strategy because of uncertainty in aetiology. Animal model is an excellent tool to investigate the mechanism, prevention and treatment on diseases. Currently, although several TMJ-OA animal models have been established, there are almost no comparative studies on different models, which poses a great challenge for selecting suitable models. OBJECTIVE: To compare three TMJ-OA induction methods and assess their applicability considering pathological changes in the cartilage, subchondral bone, osteoclasts, and synovium. METHODS: Murine models were employed and followed for 3 and 6 weeks after experimental procedures (surgery, injection, crossbite). The TMJ changes were evaluated by Safranin-O/Fast green staining, immunofluorescence staining, micro-CT, TRAP staining, and HE staining. RESULTS: In the Surgery group, a pronounced drop in bone volume fraction was observed. In the Injection group, chondrocytes were mostly disordered or arranged in clusters and a substantial increase in the OARSI score and osteoclasts was found. The OARSI score and osteoclasts also increased significantly in the Crossbite group, although to a lower extent compared with injection. CONCLUSION: Osteoarthritis-like changes were observed in all models. Concerning the applicability of the different induction methods, surgery might be an important resource for the assessment of post-traumatic TMJ-OA and subchondral bone changes in early stages. Injection induces a severe end-stage osteoarthritis in a short time and provides model basis for advanced TMJ-OA. Crossbite might be more reasonable model to explore the pathogenesis mechanism of temporomandibular arthritis due to occlusal disorders.

HO-1 in Bone Biology: Potential Therapeutic Strategies for Osteoporosis.

Osteoporosis is a prevalent bone disorder characterized by bone mass reduction and deterioration of bone microarchitecture leading to bone fragility and fracture risk. In recent decades, knowledge regarding the etiological mechanisms emphasizes that inflammation, oxidative stress and senescence of bone cells contribute to the development of osteoporosis. Studies have demonstrated that heme oxygenase 1 (HO-1), an inducible enzyme catalyzing heme degradation, exhibits anti-inflammatory, anti-oxidative stress and anti-apoptosis properties. Emerging evidence has revealed that HO-1 is critical in the maintenance of bone homeostasis, making HO-1 a potential target for osteoporosis treatment. In this Review, we aim to provide an introduction to current knowledge of HO-1 biology and its regulation, focusing specifically on its roles in bone homeostasis and osteoporosis. We also examine the potential of HO-1-based pharmacological therapeutics for osteoporosis and issues faced during clinical translation.

Hyoid Bone Position in Patients with and without Temporomandibular Joint Osteoarthrosis: A Cone-Beam Computed Tomography and Cephalometric Analysis.

OBJECTIVE: To assess the differences in hyoid bone position in patients with and without temporomandibular joint osteoarthrosis (TMJOA). METHODS: The present cross-sectional study was conducted in 427 participants whose osseous status was evaluated using cone-beam computed tomography and classified into normal, indeterminate osteoarthrosis (OA), and OA. The hyoid bone position and craniofacial characteristics were evaluated using cephalograms. Patients were divided into the normal group (N = 89), indeterminate OA group (N = 182), and OA group (N = 156). Descriptive statistics, one-way analysis of variance, and age- and sex-based stratified analyses were performed. P < 0.05 was considered statistically significant. RESULTS: The differences in Hy to MP, Hy-RGn, Hy to C3-RGn, C3-RGn, and Go-Hy-Me among the three groups were statistically significant. The differences in the Frankfort-mandibular plane angle, saddle angle, articular angle, gonial angle, ramus height, and posterior facial height were statistically significant. After adjusting age and sex, the Hy-RGn and C3-RGn in the normal group were significantly greater than the OA group. No statistical differences were observed in the hyoid measurements in the stratified analyses in males or subjects less than 18 years old. The differences in Hy to MP, Hy to C3-RGn, and Go-Hy-Me in female patients among the three groups were statistically significant. The differences in Hy to SN, Hy to FH, Hy to PP, Hy to MP, Hy-RGn, Hy-C3, Hy to C3-RGn, Go-Hy-Me, Hy-S, and C3-Hy-S in adults were statistically significant. CONCLUSION: The differences in the hyoid bone position, mainly relative to the mandible, were statistically significant in patients with or without TMJOA. The difference pattern varied among different age and sex groups. Clinical evaluation of the hyoid position must consider the age and sex of patients. Longitudinal studies are required to clarify the causal relationship between TMJOA and hyoid bone position.

d-mannose attenuates lipopolysaccharide-induced osteolysis via CPT1A-Mediated lipid metabolic regulation in macrophages.

Inflammatory osteolysis is usually linked to the activation of proinflammatory macrophage and the consequent excessive osteoclast formation. Emerging evidence indicates that agents or drugs targeting lipid metabolism in macrophages might be potential in the prevention and treatment of osteolysis. d-mannose, as a natural-existed metabolic regulator, exerts strong effects on attenuating osteopenia and inflammation. However, whether d-mannose is therapeutically effective on osteolysis and whether a metabolic mechanism counts for the effect remain to be addressed. Here, by using an in vivo lipopolysaccharide (LPS)-induced inflammatory osteolysis mouse model as well as an in vitro LPS-induced inflammatory macrophage culture system, we show that d-mannose attenuates inflammatory osteolysis and inhibits excessive osteoclastogenesis by reversing the LPS-induced activation of proinflammatory macrophage. Mechanically, d-mannose recovers LPS-suppressed Cpt1a transcription and promotes lipid metabolism of macrophage. Treatment with etomoxir, an inhibitor of CPT1A, abolishes the effects of d-mannose on LPS-treated macrophage in vitro and eliminates its protection against osteolysis in vivo. Collectively, our results imply that d-mannose attenuates LPS-induced osteolysis by manipulating CPT1A-mediated lipid metabolism in macrophages. Our results disclose the unrecognized utilization of d-mannose as an effective intervention against inflammatory osteolysis and provide evidence to manage inflammatory scenarios by therapeutically targeting lipid metabolism in macrophage.

D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner.

OBJECTIVES: Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D-mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether D-mannose interferes in chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. MATERIALS AND METHODS: In vivo anterior cruciate ligament transection (ACLT)-induced OA mouse model and an in vitro study of chondrocytes in an OA microenvironment induced by interleukin-1ß (IL-1ß) exposure were employed. Combined with Epas1 gene gain- and loss-of-function, histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability and flow cytometry experiments were performed to evaluate the chondroprotective effects of D-mannose in OA progression and the role of hypoxia-inducible factor 2 alpha (HIF-2 α) in D-mannose-induced ferroptosis resistance of chondrocytes. RESULTS: D-mannose exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviated OA progression. HIF-2α was identified as a central mediator in D-mannose-induced ferroptosis resistance of chondrocytes. Furthermore, overexpression of HIF-2α in chondrocytes by Ad-Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. CONCLUSIONS: D-mannose alleviates osteoarthritis progression by suppressing HIF-2α-mediated chondrocyte sensitivity to ferroptosis, indicating D-mannose to be a potential therapeutic strategy for ferroptosis-related diseases.

Neuroimmune interactions in painful TMD: Mechanisms and treatment implications.

The underlying mechanisms and treatment of painful temporomandibular disorders (TMDs) are important but understudied topics in craniofacial research. As a group of musculoskeletal diseases, the onset of painful TMD is proved to be a result of disturbance of multiple systems. Recently, emerging evidence has revealed the involvement of neuroimmune interactions in painful TMD. Inflammatory factors play an important role in peripheral sensitization of temporomandibular joint (TMJ), and neurogenic inflammation in turn enhances TMJs dysfunction in TMD. Furthermore, centralized neuroimmune communications contribute to neuron excitability amplification, leading to pain sensitization, and is also responsible for chronic TMD pain and other CNS symptoms. Therapeutics targeting neuroimmune interactions may shed light on new approaches for treating TMD. In this review, we will discuss the role of neuroimmune interactions in the onset of painful TMD from the peripheral and centralized perspectives, and how understanding this mechanism could provide new treatment options. Insights into the neuroimmune interactions within TMJs and painful TMD would broaden the knowledge of mechanisms and treatments of this multifactorial disease.