Poly(p-coumaric acid)nanoparticles alleviate temporomandibular joint osteoarthritis by inhibiting chondrocyte ferroptosis

Oxidative stress and inflammation are key drivers of osteoarthritis(OA)pathogenesis and disease progression.Herein we report the synthesis of poly(p-coumaric)nanoparticles(PCA NPs)from p-courmaic acid(p-CA),a naturally occurring phytophenolic acid,to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis(TMJOA).Compared to hyaluronic acid(HA)that is clinically given as viscosupplementation,PCA NPs exhibited long-term efficacy,superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA.Notably,TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis,while reducing inflammation,oxidative stress,matrix degradation,and chondrocyte ferroptosis.Overall,our study demonstrates a multifunctional nanoparticle,synthesized from natural p-coumaric acid,that is stable and possess potent antioxidant,anti-inflammatory properties and ferroptosis inhibition,beneficial for treatment of TMJOA.

Clinical Evaluation of Platelet Rich Growth Factors (PRGFS) in Treatment of Temporomandibular Joint Disc Displacement—Study Report

Objective: The aim of the study was to evaluate the effect of platelet rich growth factors (PRGFs) in treatment of temporomandibular joint disc displacement. Materials and Methods: The study subjects included 8 females having bilateral anterior disc displacement with reduction and 1 female having bilateral anterior disc displacement without reduction with the age range between 20 - 35 years. The process of obtaining PRGFs was carried out following the Anitua Technique. Results: Clinical parameters of Interincisal distance, Lateral excursion of mandible using digital caliper in millimeters and Visual Analogue Scale (VAS 0/10) for pain intensity score were used. All of these parameters were running through the intervals of two, four, and eight weeks till the end of the follow-up period at twenty-six weeks (six months). The participated patients showed the clinical improvement in the different clinical statuses such as interincisal distance;lateral excursion of mandible and Pain Score. Conclusion: the study reported early efficacy of PRGFs after the arthrocentesis of the joint in treatment of TMJ disc displacement, and according to our results, the injection of PRGFs could be a possible alternative treatment for patients who did not respond to standard treatment.

脱落乳牙牙髓干细胞来源外泌体对大鼠TMJ OA软骨下骨稳态的影响

目的:探讨关节腔内注射脱落乳牙牙髓干细胞外泌体(SHED-EXO)对大鼠颞下颌关节骨关节炎(TMJ OA)软骨下骨稳态的影响。方法:36只雄性SD大鼠随机分为3组(n=12):对照组(CON组)、碘乙酸钠(MIA)诱导TMJ OA组(MIA组)和SHED-EXO治疗TMJ OA组(治疗组)。治疗2、6周后取材,Micro-CT、荧光双标、TRAP染色、免疫组化染色和免疫荧光染色检测成骨与破骨情况,qRT-PCR检测ADAMTs5,IL-1β,OCN,OPG/RANKL等相关因子表达变化。结果:MIA组骨量丧失明显,骨髓腔明显扩大,相较于CON组,BV/TV和Tb.Th降低(P<0.001),BS/BV、Tb.Sp和Tb.N升高(P<0.01),且5 d内骨生成速率低于对照组(P<0.001);SHED-EXO组与MIA组相比,骨形态与骨量显著增加,BV/TV和Tb.Th升高(P<0.01),BS/BV、Tb.Sp和Tb.N降低(P<0.05),骨生成速率增加(P<0.01)。2、6周后,MIA组较对照组与治疗组,下骨内破骨细胞数量均升高(P<0.01),而H型血管与OCN阳性面积减少(P<0.01)。结论:关节腔注射SHED-EXO可以通过促进成骨和抑制破骨调节TMJ OA大鼠髁突软骨下骨稳态。

Distribution of pericellular matrix molecules in the temporomandibular joint and their chondroprotective effects against inflammation

The objectives of this study were to （1） determine the distribution and synthesis of pericellular matrix （PCM） molecules （collagen VI, collagen IV and laminin） in rat temporomandibular joint （TMJ） and （2） investigate the effects of PCM molecules on chondrocytes against inflammation in osteoarthritis. Four zones （fibrous, proliferating, mature and hypertrophic） of condylar cartilage and three bands （anterior, intermediate and posterior） of disc were analysed by immunohistochemistry for the presence of PCM molecules in rat TMJs. Isolated chondrocytes were pre-treated with PCM molecules before being subjected to interleukin （IL）-II~ treatment to stimulate inflammation. The responses of the chondrocytes were analysed using gene expression, nitric oxide release and matrix metalloproteinase （MMP）-13 production measures. Histomorphometric analyses revealed that the highest areal deposition of collagen VI （67.4%）, collagen IV （45.7%） and laminin （52.4%） was in the proliferating zone of TMJ condylar cartilage. No significant difference in the distribution of PCM molecules was noted among the three bands of the TMJ disc. All three PCM molecules were expressed intracellularly by chondrocytes cultured in the monolayer. Among the PCM molecules, pre-treatment with collagen VI enhanced cellular proliferation, ameliorated IL-lp-induced MMP-3, MMP-9, MMP-13 and inducible nitric oxide synthase gene expression, and attenuated the downregulation of cartilage matrix genes, including collagen I, aggrecan and cartilage oligomeric matrix protein （COMP）. Concurrently, collagen VI pretreatment inhibited nitric oxide and MMP-13 production. Our study demonstrates for the first time the distribution and role of PCM molecules, particularly collagen VI, in the protection of chondrocytes against inflammation.

Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis

There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β(TGF-β)signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder(TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease(CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by μCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen(Col X), p-Smad2/3 a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-βsignalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.

Imaging of the temporomandibular joint: An update

Imaging of the temporomandibular joint(TMJ) is continuously evolving with advancement of imaging technologies. Many different imaging modalities are currently used to evaluate the TMJ. Magnetic resonance imaging is commonly used for evaluation of the TMJ due to its superior contrast resolution and its ability to acquire dynamic imaging for demonstration of the functionality of the joint. Computed tomography and ultrasound imaging have specific indication in imaging of the TMJ. This article focuses on state of the art imaging of the temporomandibular joint. Relevant normal anatomy and biomechanics of movement of the TMJ are discussed for better understanding of many TMJ pathologies. Imaging of internal derangements is discussed in detail. Different arthropathies and commontumors are also discussed in this article.

A study of the temporomandibular joint during bruxism

A finite element model of the temporomandibular joint （TMJ） and the human mandible was fabricated to study the effect of abnormal loading, such as awake and asleep bruxism, on the articular disc. A quasilinear viscoelastic model was used to simulate the behaviour of the disc. The viscoelastic nature of this tissue is shown to be an important factor when sustained （awake bruxism） or cyclic loading （sleep bruxism） is simulated. From the comparison of the two types of bruxism, it was seen that sustained clenching is the most detrimental activity for the TMJ disc, producing an overload that could lead to severe damage of this tissue.

Chronic inflammation deteriorates structure and function of collagen fibril in rat temporomandibular joint disc

Collagen is the building component of temporomandibular joint(TMJ) discs and is often affected by inflammation in temporomandibular disorders. The macromechanical properties of collagen are deteriorated by chronic inflammation. However,the mechanism by which inflammation influences disc function remains unknown. The relationship between the ultrastructure and nanomechanical properties of collagen in inflamed discs should be clarified. Seven-week-old female Sprague–Dawley rats were randomly divided into two groups. Chronic TMJ inflammation was induced by intra-articular injection of complete Freund's adjuvant, and samples were harvested after 5 weeks. Picrosirius staining revealed multiple colours under polarized light, which represented alternative collagen bundles in inflamed discs. Using atomic force microscopy scanning, the magnitude of Young's modulus was reduced significantly accompanied with disordered collagen fibril arrangement with porous architecture of inflamed discs. Transmission electron microscopy scanning revealed a non-uniform distribution of collagen fibres, and oversized collagen fibrils were observed in inflamed discs. Fourier transform infrared microspectroscopy revealed a decrease in 1 338 cm^(-1)/amide II area ratio of collagen in different regions. The peak positions of amide I and amide II bands were altered in inflamed discs,indicating collagen unfolding. Our results suggest that sustained inflammation deteriorates collagen structures, resulting in the deterioration of the ultrastructure and nanomechanical properties of rat TMJ discs.

Topology Optimization and Fatigue Analysis of Temporomandibular Joint Prosthesis

Treatment of bone tumors in the mandible often involves extensive excavation of affected bone, followed by mandibular reconstruction. Prosthetic implants may be needed to restore jaw functionality. The challenges of making prosthetic bone implants include stress shielding and extending the mechanical life of the implant. We have developed a design algorithm to improve the efficiency of prosthesis design. A finite element model of the patient case is constructed from a computer tomography scan, and the computer implements topology optimization techniques to design the prosthesis with limited stress shielding affected by highly biomechanical compatibility. Topology optimization facilitates the design of low weight structures by automatically introducing holes into the structure. This is governed by engineering predetermined constraints to meet certain job specifications. Such a design will be tested for fatigue life before it is ready to be manufactured and used. Topology optimization can be performed as a design process to achieve a final design that takes stress shielding into consideration. The problem of stress shielding is solved by matching the stiffness of the orthopedic implant to the original bone that is being replaced. The material we used was titanium alloy (Ti-6Al-7Nb). Volume fraction of the orthodox implant was used (0.2872 for the studied case) as volume constraints. Compliance of the bulk bone was set as a further constraint to match the stiffness of the bone with the designed structure. Our results show a good life expectancy for the designed parts, with 12% higher life expectancy for stress-based topology optimization than for compliance-based topology optimization.

Septic Arthritis of the Temporomandibular Joint without an Apparent Source of Infection: A Case Report

Septic arthritis of the temporomandibular joint (TMJ) is a rare disease that is characterized by preauricular pain, edema, malocclusion, trismus and abscess formation in the TMJ region. An 85-year-old male visited our hospital with the complaint of left-sided TMJ swelling, pain and trismus. Septic arthritis of the left TMJ was diagnosed on the basis of considerable elevation of CRP (Creactive proteins) and CT imaging findings. The patient was treated with oral Faropenem at 450 mg daily, but CRP increased three days after the initial visit. He was hospitalized and treated with intravenous administration of cefazolin at 2 g and clindamycin at 1.2 g daily for six days. Propionibacterium species and Veillonella species grew in a culture of the joint aspirate, but there was no apparent source of infection. After acute infectious symptoms had passed, the patient was treated with oral amoxicillin at 750 mg daily for eight weeks and was instructed to do jaw opening exercise. The patient was discharged on the 11th hospital day. After three weeks of the hospital discharge, the patient healed completely. To avoid serious complications, clinicians should include septic arthritis of the TMJ in the differential diagnosis of preauricular pain, trismus and swelling.

Orthodontic retreatment of an adult woman with mandibular backward positioning and temporomandibular joint disorder:A case report

BACKGROUND The role of occlusal factors on the occurrence of temporomandibular joint disorders(TMDs)is still unclear and it is tricky for orthodontists to treat malocclusions in patients with TMDs.We report the case of the second orthodontic treatment of an adult female with Class II division 2 malocclusion associated with TMD.With the removal of anterior occlusal interference,TMD symptoms were alleviated and cone beam computed tomography(CBCT)images showed the bilateral condyles shifted forward.CASE SUMMARY This case report presented an orthodontic retreatment of an adult female with TMD and mandibular backward positioning based on CBCT examination and Joint Space Index(JSI)analysis.The left and right JSI values of-38.5 and-52.6 indicated that the position of bilateral condyles had posterior displacement.Ten years prior to this evaluation,she underwent orthodontic treatment resulting in the extraction of two upper premolars and one lower central incisor.The joint symptoms,including pain and sounds,were alleviated along with verified mandibular forward repositioning by extraction of another lower central incisor.CONCLUSION Mandibular backward positioning could be associated with TMD.JSI analysis based on CBCT is a convenient way to examine condylar positions quantitatively.

Treatment of condylar osteophyte in temporomandibular joint osteoarthritis with muscle balance occlusal splint and long-term follow-up:A case report

BACKGROUND Condylar osteophytes,a remodeling form of temporomandibular joint osteoarthritis(TMJ OA),mainly manifest as marginal angular outgrowths of the condyle.Previous researchers have advocated surgical removal of condylar osteophytes.Reports on the effect of occlusal splint on TMJ OA patients’joints have mostly focused on treatment with this splint,which can reduce the absorption of the affected condyle and promote repair and regeneration.However,the effect of the splint on the dissolution of condylar osteophytes has not yet been reported.CASE SUMMARY A 68-year-old female patient suffered from occlusal discomfort with left facial pain for 2 years.Cone beam computed tomography showed a rare osteophyte on top of her left condyle.She was finally diagnosed with TMJ OA.The patient refused surgical treatment and received conservative treatment with a muscle balance occlusal splint.The pain experienced by the patient on the left side of her face was relieved,and her chewing ability recovered after treatment.The osteophyte dissolved,and the condylar cortex remained stable during long-term follow-up observations.CONCLUSION The muscle balance occlusal splint could be a noninvasive means of treating condylar osteophytes in TMJ OA patients.

Effectiveness of Mesotherapy on Temporomandibular Joint Disorders

TMJDs （Temporomandibular joint disorders） are a common pathology but best treatment remains unclear. The goal of this study was to evaluate the effectiveness of mesotherapy on TMJD. We conducted a case review of all TMJD patients treated since 2006 with mesotherapy procedures only and using a cocktail of drugs composing of lidocaine, piroxicam and pentoxifylline. Patients were treated every 15 days until symptomatic relief was achieved and thereafter every two months. Main outcome was complete symptomatic relief, and associated factors were analysed. 27 patients were included. Complete pain relief was achieved in 26. The necessary number of procedures to get pain relief ranged from 1 to 6 （median of 1） and the total number of treatments from 1 to 40 （median of 11）. 19 patients had other painful complains mainly related with anxiety disorders. A weak correlation （r = 0.357; p = 0.05） between anxiety disorders and the required months of treatments was found. Mesotherapy is a valuable option on pain relief in a temporomandibular pain syndrome with none of the systemic effects of oral medication. Anxiety may have a role on the aetiology and therapeutic success highlights the holistic approach of these patients. Future comparative studies are necessary.

Multidetector computed tomography of temporomandibular joint: A road less travelled

This article reviews the imaging anatomy of temporomandibular joint(TMJ), describes the technique of multi-detector computed tomography(MDCT) of the TMJ, and describes in detail various osseous pathologic afflictions affecting the joint. Traumatic injuries affecting the mandibular condyle are most common, followed by joint ankylosis as a sequel to arthritis. The congenital anomalies are less frequent, hemifacial microsomia being the most commonly encountered anomaly involving the TMJ. Neoplastic afflictions of TMJ are distinctly uncommon, osteochondroma being one of the most common lesions. MDCT enables comprehensive evaluation of osseous afflictions of TMJ, and is a valuable tool for surgical planning. Sagittal, coronal and 3D reformatted images well depict osseous TMJ lesions, and their relationship to adjacent structures.

Pigmented Villonodular Tenosynovitis of the Temporomandibular Joint—A Case Report

Background: Pigmented villonodular synovitis is a rare condition typically affecting the major joints and the involvement of the temporomandibular joint is rare. Although, it is histologically benign, it can be locally aggressive, capable of extensive bone destruction. The disease has aggressive behavior and a high incidence of recurrence (40% - 60%). Case report: A 35 years old male presented with history of unilateral hearing loss and otalgia of six month duration. On examination, there was a soft bulge in the superior wall of external auditory canal. Contrast enhanced CT scan showed soft tissue density occupying the right external auditory canal and bulging into the middle ear cavity, displacing the intact ossicular chain medially with evidence of destruction of the posterior wall of the external auditory canal, glenoid fossa, mastoid bone and the scutum. The squamous part of the right temporal bone showed evidence of lateral bowing with discontinuity. Surgical resection was done through post aural approach. Histopathological examination revealed pigmented villonodular tenosynovitis which stained positive for CD 68. Post operatively patient was evaluated clinically and with radiological modalities which showed healthy mastoid cavity and no increase in post operative granulations on magnetic resonance imaging. Conclusion: Pigmented villonodular tenosynovitis of temporomandibular joint is a rare entity. Due to the aggressive behavior of the lesion, radical or aggressive surgical resection should be done. Long term follow up with radiological modality should be done due to the high recurrence rate.

Management of disorder of temporomandibular joint syndrome using elastic resin occlusal pad: a clinical observation

Objective To investigate the possibility of occlusal pad in treating disorder of temporomandibular joint syndrome.Methods We treated 25 patients with disorder of temporomandibular joint syndrome using occlusal pad made of elastic resin,and evaluated the effects.Results Total effective rate was 96%.Clicking and pain dissappeared in all patients.Conclusion Occlusal pad made of elastic resin could be used for treating disorder of temporomandibular joint syndrome in clinic.

Future of Treatment of Temporomandibular Joint Dysfunctions in Parkinsonian Patients

The purpose of the study was designed to clarify the modern trends of physical therapy in treatment of temporomandibular joint dysfunctions in Parkinsonian patients, which in this respect included the degree of pain, the muscles power of both masseter and pterygoid, the range of TMJ motion, the angle of mouth opening and their effects on electromyography study in both sexes. Subjects: Thirty males and females were the same degree of disabilities according to modified Hoehn and Yahr scales (grade 3) of Parkinsonian patients, and their age ranged from 50 - 77 years old and their weight ranged from 60 - 88 kg. They were randomly divided into two equal groups (G1 and G2). G1 (control) consisted of 15 patients of both sexes and was treated by exercises therapy program and G2 (experimental) consisted of 15 Parkinsonian patients of both sexes and was treated by the same exercises therapy program and low level pulsed electromagnetic therapy. Vital signs such as blood pressure, body temperature, pulse rate and respiratory rate were measured before and after the treatment sessions. Assessments: Visual analogue scale was used to measure degree of pain. Tensiometer was used to measure the muscle power of masseter and pterygoid, the digital goniometer was used to investigate the range of TMJ movement. Moreover, standard electromyography test (EMG) was used to measure the compound muscle action potentials. Statistically the results for all groups were analyzed by t-test to compare the differences between the two groups. The statistical package of social sciences (SPSS, version 10) was used for data processing using the P-value 0.05 as a level of significance. Results showed that there were significant improvements in all variables in G2 only. However, there was a little improvement but not significant in both G1. Therefore, it could be concluded that the use of low level pulsed electro-magnetic therapy combined with exercises program was the good method to control pain of TMJ, increase of muscle power and the range of their movements together with determination of electro-myography. Our results opened a new link to manage the TMJ dysfunctions in Parkinsonian patients via the use of low level pulsed electromagnetic therapy combined with exercises program.

Rheumatoid Arthritis of the Temporomandibular Joint;Comparison of Digital Panoramic Radiographs Taken Using the Joint Limitation Program [JLA View] and CT Scans

Objective: The aim of this study was to evaluate the efficacy of digital panoramic radiographs using the JLA view pro-gram in cases of rheumatoid arthritis and compare them to CT scans of the patients. Methods: 40 patients with known condition of RA and clinical symptoms in the TMJ were selected for the study. Radiological evaluation included a panoramic radiograph of the TMJs that was taken and a computer tomography of the joints. In the panoramic radio-graphs taken, isolation of the TMJs was done using the JLA view program, while in the CT scans of the patients, all scans were taken with closed mouth, with a distance of 0.5 mm per slice. The parameters examined were: 1) Bony changes of the condyle;2) The position of the condyle in the mandibular fossa;3) The joint space;4) Bony changes of mandibular fossa. Results: There were no statistically significant differences found between the two observers or be-tween the two joints of the same patient [right and left] on the panoramic radiographs. For the case of CT scans there were significant differences between the joint space of right and left joints, while in the ANOVA performed differences were found for the evaluation of the bony changes of the condyle. Conclusion: There were no significant differences between the two radiographic methods selected and therefore when a proper simple radiograph is taken and well evalu-ated, the conclusions drawn from it are well based and there is no need for further

Structural optimization of patient-specific temporomandibular joint replacement implants for additive manufacturing:novel metrics for safety evaluation and biomechanical performance

Total temporomandibular joint(TMJ)replacement is recommended only when there is irreversible damage to the joint and no conservative treatment can provide functional improvements.Several stock and custom-made TMJ implants have been made available;however,retrospective and comparative studies were unable to find significant differences between the two types of solutions.The introduction of additive manufacturing(AM)techniques in medical practice allows for a greater freedom of design and a higher degree of device customisation.The combination of AM with structural optimisation may streamline development and provide the key for fabricating biomechanic ally enhanced TMJ implants.In this study,structural optimis ation techniques were applied to develop and numerically validate a patient-specific TMJ implant.The biomechanical behaviour of each intermediate TMJ design was assessed under four different nominal and maximum biting tasks using finite element analyses.In addition,a new set of metrics were proposed to compare each design regarding biomechanical performance and implant safety.The results suggest that 55-82%of the natural/intact strain patterns can be recovered with the finally selected TMJ implant.This represents an increase of 15%in biomechanical performance for incisor biting,15%for right molar biting,17%for left molar biting and a decrease of 2%for left group biting compared with the initial design.The results also suggest that load transfer at the proximal ramus reduces the implant’s impact on the mandible’s strain patterns.Finally,structural optimisation allows for a volume reduction of up to 44%with a minimum loss of implant safety and biomechanical performance.

Treatment of Chronic Temporomandibular Joint Pain and Sleep Disordered Breathing by Teledontic and Telegnathic Protocol Utilizing Total Joint Replacement

Orthopedic clinicians frequently encounter patients with temporomandibular joint (TMJ) pain and associated sleep disordered breathing (SDB) that coexists with the patient’s orthopedic conditions. The systemic effects and associated comorbidities caused by TMJ and associated SDB are commonly not recognized as potential contributors to the patient’s long-term orthopedic outcome. This article describes a comprehensive and interdisciplinary medical dental treatment, which was able to successfully address patient’s severe chronic TMJ, head, neck and shoulder pain as well as other health concerns including SDB. Moreover, a new teledontic and telegnathic treatment protocol and principles utilizing total joint replacement for care of patients with chronic TMJ pain and SDB will be introduced describing a completed case.