BackgroundMalocclusion has been associated with alterations in central nervous system function; however, the effects of persistent abnormal occlusal input on whole-brain functional organization remain poorly understood. This study aimed to investigate functional brain network reorganization associated with unilateral anterior crossbite (UAC) in rats.MethodsFourteen female rats were used, seven of which were treated with left-sided UAC at 6 weeks old and the other seven served as sham-operation controls. Resting-state functional magnetic resonance imaging data were acquired at 26 weeks old. Regional activity in the proprioceptive pathway was assessed, followed by graph theoretical analysis of whole-brain functional networks.ResultsUAC rats exhibited altered regional activity in the right ventral posteromedial thalamus (p = 0.023) and primary somatosensory cortex (p < 0.001), contralateral to the modeling side. Network analysis revealed significantly higher normalized clustering coefficient (p = 0.014) and small-worldness (p = 0.006) in the UAC group compared with controls. Furthermore, UAC rats showed enhanced functional connectivity within a subnetwork (p = 0.023) in which the right amygdala exhibited the greatest number of altered connections. In addition, abnormal regional activity was also detected in the right amygdala of UAC rats (p = 0.039).ConclusionLong-term UAC in rats is associated with alterations in whole-brain functional network organization. These findings provide new insights into the central neural responses associated with abnormal occlusal input.

Occlusion refers to the contact relationship between the upper and lower teeth.Its biomechanical properties influence motor function,most often in the orofacial and cervical regions,and the patient's psychological well-being as well.In this review,we summarized age-related changes in occlusion and the corresponding clinical management and preventive strategies from three perspectives—the functional characteristics of normal occlusion and their age-related changes,the effects of abnormal occlusion on health and the potential neurophysiological mechanisms involved,and age-related changes in occlusion and the corresponding preventive and therapeutic approaches.Abnormal wear of the occlusal surfaces alters the biomechanical relationship of occlusion.Animal studies have shown that abnormal biomechanical occlusion may result in the following problems:1)periodontal trauma;2)dysfunction of the orofacial and cervical muscles and vagus nerve-related visceral motor dysfunction through synaptic connections between neurons in the mesencephalic trigeminal nucleus and motor neurons in the trigeminal motor,facial,accessory,hypoglossal,and dorsal vagal nuclei;and 3)psychological responses such as anxiety,mediated via effects on neuronal activity in the lateral habenular nucleus.The wear coefficients of dental restorative prostheses differ from those of natural teeth.Long-term use of dental prostheses increases the risk of wear mismatch between natural and artificial teeth,which may lead to increased risk of occlusal interference.Tooth wear is the most common manifestation of age-related changes in occlusion.In addition to malocclusion,missing teeth,and pre-existing prostheses,many older patients also present with periodontal disease.Prolonged failure to replace missing teeth may lead to progressive occlusal disturbances,characterized by tilting of adjacent teeth and elongation of opposing teeth.When age-related wear is superimposed on malocclusion,periodontal disease,and missing teeth,it not only exacerbates the adverse health effects of abnormal occlusion but also substantially complicates treatment.Therefore,early diagnosis and treatment of malocclusion and periodontal diseases are essential to the prevention of situations where orthodontic intervention becomes extremely challenging in old age.Missing teeth should be restored promptly to prevent secondary occlusal disorders.For dental prostheses,careful attention should be paid to material selection and biomechanical design.Excessively hard materials should be avoided to prevent the development of interfering occlusal contacts.In addition,prostheses should be replaced regularly to reduce occlusal problems arising from uneven physiological wear and the associated secondary health consequences.

Background The association between occlusion and temporomandibular disorders (TMD) remains obscure. The present purpose was to explore the asymmetrical occlusion feature(s) potentially linked to TMDs. Methods This study enrolled 148 patients with a chief complaint of malocclusion. Of those, 84 had no signs of TMD (Group-ORD1), and 64 had signs of TMD (Group-ORD2). An additional 84 patients with a chief complaint of TMD symptoms and a history of orthodontic therapy were included (Group-TMD). All patients in the study were female. Asymmetry of six occlusion variables was measured on plaster study casts and recorded as 1 for asymmetry and 0 for symmetry. The variables contain the sagittal asymmetry: the first molar mesial-distal relationship (F1), canine mesial-distal relationship (F2); the horizontal asymmetry: anterior overjet and overbite relationship (F3), posterior overjet and overbite relationship (F4); missing teeth (F5), and the weight of the asymmetrical occluding pair (F6). And logistic regression model was used for data analyses. Results In the analyses for Group-ORD2 versus Group-ORD1, the F6 variable and the interactions of F1*F2 and F1*F2*F6 were entered into the model (all OR > 2.68). For Group-TMD versus Group-ORD1, the variables were F1, F5, and F6 (all OR > 2.39) and F4 (OR = 0.28), and the interactions were F5*F6, F1*F2*F6, F1*F5*F6, and F1*F2*F5*F6 (all OR > 2.78) and F2*F4, F3*F5, and F2*F4*F6 (all OR < 0.13). For Group-TMD versus Group-ORD2 the variables and interactions were F5, F5*F6, and F1*F5*F6 (all OR > 4.03) and F4, F4*F6 and F2*F4*F6 (all OR < 0.21) (all P < .05). Conclusions Patients with sagittal asymmetry, asymmetrical missing teeth, or asymmetrical weight of contact have a higher prevalence of TMD.

OBJECTIVE:To investigate the parathyroid hormone-related peptide (PTHrP) nuclear localisation segment (PTHrP-NLS) and parathyroid hormone 1 receptor (PTH1R) signal-dependent rehabilitative effects of CD90+ chondrocytes (CD90-CCs) on degenerative temporomandibular joint (TMJ) cartilage. DESIGN:Changes in PTHrP and PTH1R expression in CD90-CCs in TMJ cartilage in response to bilateral anterior elevation (BAE), which promotes TMJ cartilage thickening, were measured in female mice. A genetic modulation strategy was adopted. CD90-CCs were isolated from PTHrP-NLS conditional mutation (CD90-CreER;Pthlh84STOP) mice, PTH1R conditional mutation (CD90-CreER;Pth1r-/-) mice, human osteoarthritic knee cartilage (7 surgery operation donors) and rat osteoarthritic TMJ cartilage. These isolated CD90-CCs were cultured, amplified, and then injected into the experimental osteoarthritic TMJ, which was induced by the unilateral anterior crossbite (UAC) method, to evaluate the rehabilitative effect of the CD90-CCs (all, n = 6). RESULTS:BAE increased the TMJ cartilage thickness and the expression of PTHrP and PTH1R. The cartilage thickening effect of BAE was retarded in PTHrP conditional mutation (CD90-CreER;Pthlh-/-) mice and CD90-CreER;Pth1r-/- mice. Local injections of CD90-CCs reversed 62.96% of the UAC-induced cartilage loss [95% CI: (46.93%, 78.99%)], whereas the rescue effect of CD90-CCs derived from CD90-CreER;Pthlh84STOP mice and CD90-CreER;Pth1r-/- mice was limited. CD90-CCs from osteoarthritic TMJ cartilage and osteoarthritic knee cartilage, both of which express PTHrP and PTH1R, also produced rehabilitative effects. CONCLUSIONS:The restorative effects of CD90-CCs on cartilage are controlled by PTHrP-NLS and PTH1R signalling. Autologous infusion of sufficient numbers of expanded PTHrP and PTH1R dual signal-positive CD90-CCs could be a new strategy for treating joints with osteoarthritic cartilage.

Background: Bimaxillary dentoalveolar protrusion is a frequent complain in orthodontic clinic. The incisor angulation and inclination have been largely discussed. The present purpose was to assess the involvement of the teeth distal to incisors. Methods: In this cross-sectional study, 63 patients with Class I occlusion and an average sagittal relationship between the maxilla and mandible were enrolled. Twenty-two cases (20.14 +/- 7.32 years old) who had protrusion profile and flaring upper and lower incisors were diagnosed as bimaxillary dentoalveolar protrusion. The other 41 cases (21.87 +/- 7.15 years old) who had a balanced facial profile and mild anterior crowding were taken as controls. The buccolingual angulation and the mesiodistal inclination of the canines and premolars, which had single root, revealed on the cone-beam computed tomography (CBCT) images were measured. The values of the angulation and inclination were compared between the two groups by using Student t-test methods (alpha = 0.05). Results: The bilateral mandibular canines were more labially angulated (P<0.001) but the bilateral mandibular first premolars were more mesial inclined in the bimaxillary dentoalveolar protrusion group than that in the control group (for tooth 34,P < 0.002; for tooth 44, P < 0.010). Conclusions: More labial angulated mandibular canine and more mesial inclined mandibular first premolars associate with bimaxillary dentoalveolar protrusion. The labial-lingual angulation of the mandibular canines and the mesial-distal inclination of the mandibular first premolar should be paid a specially attention during the development, thus, the early intervention of the bimaxillary dentoalveolar protrusion.

OBJECTIVE:Ageing and aberrant biomechanical stimulation are two major risk factors for osteoarthritis (OA). One of the main characteristics of aged cartilage is cellular senescence. One of the main characteristics of osteoarthritic joints is cartilage degeneration. The cells in the temporomandibular joint (TMJ) cartilage are zonally arranged. The deep zone cells are differentiated from the superficial zone cells (SZCs). The purpose of the present study was to investigate whether degenerative shear stress (SS) stimulates the senescence programme in TMJ SZCs, and to determine which miRNA is involved in this process. METHOD:SZCs were isolated from the TMJ condyles of 3-week-old rats and treated with continuous passaging or SS. RNA sequencing was conducted to identify miRNA(s) that overlap with those involved in the replication senescence process and the SS-induced degeneration programme. Unilateral anterior crossbite (UAC), which is TMJ-OA inducible, was applied to 2-month-old and 12-month-old mice for 3 weeks. The effect of TMJ local injection of agomiR-708-5p was evaluated histologically. RESULTS:Both replication and SS treatment induced SZC senescence. miR-708-5p was identified. Knocking down miR-708-5p in SS-treated SZCs led to more severe senescence by alleviating the inhibitory impact of miR-708-5p on the TLR4/NF-κB pathway. miR-708-5p expression in mouse TMJ cartilage decreased with age. UAC induced more severe osteoarthritic cartilage lesions in 12-month-old mice than in 2-month-old mice. Injection of agomiR-708-5p suppressed UAC-induced osteoarthritic cartilage lesions. CONCLUSIONS:Age-related miR-708-5p deficiency is involved in the mechanically stimulated OA process. Intra-articular administration of agomiR-708-5p is a promising new strategy for OA treatment.

BACKGROUND:Aberrant occlusion and aging are two main risks for temporomandibular joint (TMJ) degeneration. OBJECTIVE:To assess the combined impact of occlusion and age on TMJ disc. METHODS:To avoid the confounding impact of gender, presently, 126 female C57BL/6J mice, 63 youngsters, 6-week old and 63 adults, 28-week old, were used. An experimental bilateral anterior crossbite (BAC) relation was created by installing metal tubes onto the mandibular incisors. Mice were sacrificed at 3, 7 and 11 weeks (n = 9). Additionally, the installed tubes were removed at 7 weeks in removal groups and the TMJs were sampled after another 4 weeks (n = 9). Disc changes were detected by histomorphology, immunohistochemistry, and western blot assays. RESULTS:Disc deformation was obvious in BAC groups. The typical change was hyperplasia at the posterior region of the disc where there was significant infiltration of inflammatory cells. Expressions of the inflammatory markers, including tumour necrosis factor-α and interleukin-1β, and the catabolic markers, including fibronectin (FN), FN N-terminal fragments, and vascular endothelial growth factor-A, were all increased. The changes were more obvious in adults than in youngsters. Removal of BAC attenuated inflammatory and catabolic changes in the youngsters, but the inflammatory markers recovered little in the adults. CONCLUSION:TMJ disc responds to BAC by degeneration and inflammation, and respond to BAC removal by rehabilitation. Adult discs show severer degeneration responses to BAC and a lower level of anti-inflammatory capability to BAC removal than the youngster's discs. Animals cannot be equated with humans. The human disc response to occlusion changes worth further exploration.

Purpose (the aim of the study): Temporomandibular joints (TMJs) have a biomechanical relationship with dental occlusion, and respond to alteration of occlusion by remodeling. We had reported that aberrant occlusion, named unilateral anterior crossbite (UAC), stimulates osteoarthritis (OA) lesions in TMJs of mice, characterized as enhanced chondrocytes differentiation and matrix loss. Piezo1 is a nonselective ion channel that exhibits a preference for Ca2+ in response to mechanical stimuli. By using Piezo1 mutation technique, presently, we aimed to identify the role of Piezo1-mediated mechanotransduction in differentiation and degenerative response of chondrocytes in TMJ cartilage to UAC.

OBJECTIVE:Abnormal mechanical stress is intimately coupled with osteoarthritis. Microtubules play a vital role in the regulation of mechanotransduction and intracellular transport. The purpose of the present study was to investigate the impact of stress-induced microtubule impairment on intracellular transport and lipid droplet (LD) accumulation in chondrocytes. METHOD:Rats were subjected to unilateral anterior crossbite (UAC), which is inducible for degeneration of temporomandibular joint (TMJ) cartilage. Chondrocytes derived from rat TMJ cartilage were subjected to fluid flow shear stress (FFSS) and analyzed via LCMS/MS-based proteomics. The microtubule destabilization agent nocodazole and/or the microtubule stabilizer docetaxel were used in the UAC and FFSS models. RESULTS:In both FFSS- and UAC-treated chondrocytes, decreased acetylated α-Tubulin (ac-Tubulin) expression and LD accumulation were observed. Proteomic data revealed increased levels of the LD-associated protein perilipin 3 (Plin3) and decreased levels of cytoskeleton components in FFSS-treated chondrocytes. Live-cell imaging revealed that the colocalization of LDs with lysosomes was significantly decreased after FFSS treatment. Impairment of microtubules by nocodazole reduced the protein level of ac-Tubulin and disrupted the Hsc70-mediated interaction between Plin3 and Lamp2a, as shown by co-IP assays. In contrast, docetaxel reversed the suppression of ac-Tubulin expression, reduced the accumulation of LDs, and decreased the expression of Plin3 in chondrocytes exposed to FFSS and UAC, and docetaxel ameliorated UAC-induced osteoarthritic lesions in the TMJ cartilage. CONCLUSION:Microtubule impairment under aberrant stress conditions disrupts intracellular transport and blocks lipophagy, causing LD accumulation in chondrocytes. Microtubule stabilization could be a new approach for treating stress-induced cartilage degeneration.

Purpose (the aim of the study): Aberrant mechanical loading is a well-documented trigger factor of osteoarthritis (OA) of which chondrocytes loss is one of the main characters. The underlying mechanism is still unclear. Cytoskeleton is important to maintain cell motility, mitosis, and protein trafficking. Tubulin microtube, one of the main constitutions of cytoskeleton, has essential roles in transferring of molecules, such as lipid. Accumulation of lipid droplets (LDs) inside cells can then be taken as a sign of cytoskeleton dysfunction.

OBJECTIVE:Some cells in temporomandibular joint (TMJ) cartilage undergo proliferation in response to negative pressure, which can be induced in vivo by creating bilateral anterior elevation (BAE). TMJ cartilage harbours CD90-expressing cells, and CD90 expression increases under certain controlled conditions. The parathyroid hormone-related peptide (PTHrP) nuclear localisation segment (NLS) promotes chondrocyte proliferation, and mammalian target of rapamycin (mTOR) signalling plays a regulatory role in promoting PTHrP transcription. The purpose of this study was to determine the role of the mTOR/PTHrP-NLS axis in the proliferative responses of CD90+ chondrocytes in TMJ cartilage to BAE. METHODS:CD90+ cells were isolated from TMJ cartilage and subjected to negative pressure followed by RNA sequencing (RNA-seq). A PTHrP-NLS conditional mutation (CD90-CreER;Pthlh84STOP-fl/fl) mouse model was developed to obtain CD90+ cell-specific PTHrP-NLS conditional mutation (Pthlh84STOP) littermate. CD90-Cre;Tsc1fl/fl mice and CD90-Cre;mTORfl/fl mice were generated to obtain Mtor conditional knockout (Mtor-CKO) and Tsc1-CKO littermates. RESULTS:Using RNA-seq, the mTOR signalling pathway was identified as the most significant biological process occurring in superficial zone cells of the TMJ condylar cartilage under negative pressure. Proliferation of CD90+ cells was stimulated in Tsc1-CKO littermates but inhibited in both Mtor-CKO and Pthlh84STOP littermates. BAE did not promote chondrocyte proliferation in either Mtor-CKO or Pthlh84STOP littermates. Administration of the PTHrP87-139 peptide to Mtor-CKO mice restored chondrocyte proliferation and rescued the promoting effect of BAE in TMJ cartilage. CONCLUSIONS:CD90+ chondrocytes in TMJ cartilage proliferate in response to negative pressure under the control of the TSC1-mTOR/PTHrP-NLS pathway.

Purpose: To analyze the poten-al associa-on between the occlusion features and the incidence of temporomandibular joint (TMJ) arthralgia in pa-ents with par-al dentures. Materials and Methods: A total of 101 par-al denture wearers were collected, 45 with unilateral TMJ arthralgia diagnosed according to the Diagnos-c Criteria for Temporomandibular Disorders (DC/TMD). Binary logis-c regression analysis was adopted. The TMJ asymptoma-c group (n = 45) was quan-fied as 0, while the TMJ arthralgia group (n = 56) was quan-fied as 1. In total, 13 occlusion variables were analyzed: gender, age, number of prosthe-c teeth, number of den--on quadrants with a prosthe-c tooth, anterior or posterior prosthesis loca-on in maxillary or mandibular den--on, occluded prosthesis pair, anterior overjet, and overbite rela-on. Simple and mul-ple binary logis-c models were adopted, accordingly, for the risk impact of them on TMJ arthralgia. Results: Overbite (OR = 2.238) and maxillary anterior prosthesis (OR = 0.305) were entered into the simple binary logis-c model; while overbite (OR = 2.774) plus maxillary anterior prosthesis (OR = 0.347), overbite (OR = 3.425) plus unilateral maxillary posterior prosthesis (OR = 4.672), and overbite (OR = 3.476) plus overjet (OR = 0.436) and mandibular anterior prosthesis (OR = 0.177) were entered into the mul-variate logis-c regression model (all, P <.05). Conclusions: Par-al denture wearers with a deep overbite, especially those with a unilateral maxill ary posterior prosthesis, had a higher prevalence of unilateral TMJ arthralgia.

Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive 1 , 2 . Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy.

The temporomandibular joint (TMJ) cartilage is biomechanical sensitive. Cells in TMJ cartilage are zonally arranged, earlier differentiated in the super zone and late differentiated in the deep zone. The purpose was to detect the zonal interdependence in TMJ cartilage under dental biomechanical stimulations. Here, we obtained the Sox9(CreER); Rosa26(tdTomato) and Col10(CreER); Rosa26(tdTomato) mice to label super zone Sox9-expressing (Sox9(+)) or deep zone Col10-expressing (Col10(+)) cells by tdTomato (TdT), and Sox9(CreER); Rosa26(DTA) and Col10(CreER); Rosa26(DTA) mice to ablate Sox9(+) or Col10(+) cells selectively. These mice were subjected to unilateral anterior crossbite (UAC) or bilateral anterior elevation (BAE) dental stimulation, which promoted terminal differentiation or proliferation of TMJ chondrocytes, respectively. In both UAC and BAE models, the Sox9-TdT(+) cells performed as proliferation and mature differentiation, showing as expressing Ki67 and Col-X, respectively; while the Col10-TdT(+) cells performed as terminal differentiation, showing as expressing osteocalcin (OCN). In both Sox9(+)- and Col10(+)-cells ablation groups, there were reductions in cell number, cartilage thickness and matrix amount, subchondral bone loss, and condylar deformation. The UAC-promoted terminal differentiation was enhanced, and the BAE-promoted cellular proliferation was ruined. Impressively, when Col10(+) cells were ablated, the UAC-promoted DAP3 expression, an anoikis marker, was further increased, while the BAE-suppressed DAP3 expression was instead greatly increased. These findings demonstrated that the cartilage zones function interdependently. The super zone harbors the cells that undergo differentiation to deep zone cells, the deep zone contains load-bearing matrix which is structural essential for the cells located inside or superficial.

目的 比较研究颞下颌关节紊乱病(temporomandibular disorders,TMD)单侧颞下颌关节疼痛患者与夜磨牙患者的咬合关系特点,为临床鉴别诊断及治疗方案的设计提供参考依据.方法 选取2015-2017年于空军军医大学第三附属医院颞下颌关节病科就诊的169例TMD单侧颞下颌关节疼痛患者(TMD组)和189例夜磨牙患者(夜磨牙组)的临床资料进行回顾性分析.对2组患者治疗前牙颌石膏模型进行测量分析,比较其错畸形分类、上下牙列中线位置、前牙覆和覆盖情况、个别牙错、个别牙错位、缺牙(第三磨牙除外)、第三磨牙萌出及口腔修复情况.结果 ①2组患者错畸形分类、上下牙列中线位置、前牙覆覆盖情况比较,差异均无统计学意义(均P＞0.05).②TMD组患者反发生率(28.4％)明显高于夜磨牙组(17.5％),差异有统计学意义(x2=6.102,P=0.014);而2组患者锁、对刃及开发生率比较,差异均无统计学意义(均P＞0.05).③TMD组上颌侧切牙伴其他牙位唇倾的占比(22.6％)明显高于夜磨牙组(4.9％),上颌中切牙伴其他牙位扭转的占比(53.3％)低于夜磨牙组(74.5％),而上颌尖牙伴其他牙位扭转的占比(37.8％)明显高于夜磨牙组(5.5％),差异均有统计学意义(均P＜0.05);而2组其他牙位错位情况比较,差异均无统计学意义(均P＞0.05).④TMD组缺牙发生率(23.7％)高于夜磨牙组(15.3％),差异有统计学意义(x2=3.974,P=0.046);在各组缺牙患者中,TMD组多颗牙缺失患者占比(47.5％)大于夜磨牙组(24.1％),夜磨牙组单颗牙缺失患者占比(75.9％)大于TMD组(52.5％),其分布差异有统计学意义(x2=3.907,P=0.048).⑤TMD组患者双侧下颌第三磨牙的萌出率均高于夜磨牙组,差异均有统计学意义(均P＜0.05);而2组上颌第三磨牙萌出率比较,差异无统计学意义(P＞0.05).⑥在各组固定义齿修复患者中,TMD组多颗修复患者占比(89.5％)大于夜磨牙组(占33.3％),夜磨牙组单颗修复患者占比(66.7％)大于TMD组(10.5％),其分布差异有统计学意义(P＜0.001).结论 TMD单侧颞下颌关节疼痛患者与夜磨牙患者的咬合特点在个别牙反、个别牙错位、缺牙(第三磨牙除外)、下颌第三磨牙萌出及口腔修复情况方面存在一定差异,可为临床鉴别诊断提供参考依据.

BACKGROUND:Joint effusion is often noticed in magnetic resonance image (MRI) and its diagnostic value for arthralgia of the temporomandibular joint (TMJ) remains obscure. OBJECTIVE:To develop a method for quantitatively evaluating the joint effusion revealed in MRI and its diagnostic value for arthralgia of the TMJ. METHODS:Two-hundreds and twenty-eight TMJs, 101 with arthralgia (Group P) and 105 without (Group NP) from 103 patients, and 22 TMJs (Group CON) from 11 asymptomatic volunteers were examined by using MRI. The effusion volume was measured after constructing a three-dimensional structure of the joint effusion revealed in MRI by using the ITK-SNAP software. The diagnostic capabilities of the effusion volume on arthralgia were evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS:Totally 146 joints showed MRI signs of joint effusion, including nine joints from Group CON. However, the medium volume was greater in Group P (66.65 mm3 ), but was much similar in Group CON (18.33 mm3 ) to Group NP (27.12 mm3 ). The effusion volume larger than 38.20 mm3 was validated to discriminate Group P from Group NP. The AUC value was 0.801 (95% CI 0.728 to 0.874), with a sensitivity of 75% and specificity of 78.9%. The median volume of the joint effusion was larger in those with than without bone marrow oedema, osteoarthritis, Type-III disc configurations, disc displacement and higher signal intensity of the retrodiscal tissue (all, p < .05). CONCLUSION:The present method for evaluate joint effusion volume well discriminated painful TMJs from non-pain ones.

The superficial zone cells in mandibular condylar cartilage are proliferative. The present purpose was to delineate the relation of calcium-sensing receptor (CaSR) and parathyroid hormone-related peptide nuclear localization sequence (PTHrP87- 139), and their role in the proliferation behaviors of the superficial zone cells. A gain-and loss-of- function strategy were used in an in vitro fluid flow shear stress (FFSS) model and an in vivo bilateral elevation bite model which showed mandibular condylar cartilage thickening. CaSR and PTHrP87- 139 were modulated through treating the isolated superficial zone cells with activator/SiRNA and via deleting CaSR or parathyroid hormone-related peptide (PTHrP) gene in mice with the promoter gene of proteoglycan 4 (Prg4-CreERT2) in the tamoxifen-inducible pattern with or without additional injection of Cinacalcet, the CaSR agonist, or PTHrP87- 139 peptide. FFSS stimulated CaSR and PTHrP expression, and accelerated proliferation of the Prg4-expressing superficial zone cells, in which process CaSR acted as an up-streamer of PTHrP. Proteoglycan 4 specific knockout of CaSR or PTHrP reduced the cartilage thickness, suppressed the proliferation and early differentiation of the superficial zone cells, and inhibited cartilage thickening and matrix production promoted by bilateral elevation bite. Injections of CaSR agonist Cinacalcet could not improve the phenotype caused by PTHrP mutation. Injections of PTHrP87- 139 peptide rescued the cartilage from knockout of CaSR gene. CaSR modulates proliferation of the superficial zone cells in mandibular condylar cartilage through activation of PTHrP nuclear localization sequence. Our data support the therapeutic target of CaSR in promoting PTHrP production in superficial zone cartilage.