Temporomandibular Joint Condyle Research Articles

A regenerative approach for temporomandibular joint repair: An invitro and exvivo study.

Current clinical approaches to regenerate temporomandibular joint (TMJ) articulating cartilage defects only treat the symptoms (i.e. pain and dysfunction) and do not seek to restore joint integrity for long-term relief. Therefore, we investigated a novel self-assembling tissue-engineered cartilage to overcome this significant clinical issue for TMJ regenerative purposes. Examine the maturation of dynamic self-regenerating cartilage (dSRC) using auricular chondrocytes and evaluate a novel combinatorial approach with fractional laser treatment and dSRC implantation for TMJ cartilage repair. A suspension of 107 freshly harvested rabbit ear chondrocytes was cultured under a continuous reciprocating motion to form the dSRC. After 2, 4 and 8 weeks of culture, dSRC samples were stained with H&E, Safranin-O and Toluidine Blue. Immunohistochemistry (IHC) was performed for collagens type I and II. Channels (300-500 μm diameter and 1.2-1.5 mm depth) were created in six freshly harvested condyles using a fractional Erbium laser. Two groups were tested: dSRC in a laser-ablated lesion (experimental) and an empty laser-ablated channel (control). TMJ condyles were cultured for up to 8 weeks and analysed as described above. H&E staining showed a high cell density in dSRC compared to native cartilage. All dSRC groups demonstrated intense Safranin-O staining, indicating high glycosaminoglycan (GAG) production and intense Toluidine Blue staining showed high proteoglycan content. IHC confirmed that dSRC consisted predominantly of collagen type II. The experimental group showed improved cartilage repair at both time points compared to the empty channels. dSRC viability and successful matrix formation were demonstrated invitro. The combination of fractional laser ablation and dSRC implantation enhanced cartilage repair.

Key Roles of Gli1 and Ihh Signaling in Craniofacial Development.

The Hedgehog (Hh) signaling pathway orchestrates its influence through a dynamic interplay of Hh proteins, the cell surface receptor Ptch1, Smo, and Gli transcription factors, contributing to a myriad of developmental events. Indian Hedgehog (Ihh) and Gli zinc finger transcription factor 1 (Gli1) play crucial roles in developmental regulation within the Hh signaling pathway. Ihh regulates chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ). Losing Ihh results in cranial bone malformation and decreased ossification and affects the formation of cranial base cartilage unions, TMJ condyles, and joint discs. Gli1 is predominantly expressed during early craniofacial development, and Gli1+ cells are identified as the primary mesenchymal stem cells (MSCs) for craniofacial bones, crucial for cell differentiation and morphogenesis. In addition, a complex mutual regulatory mechanism exists between Gli1 and Ihh, ensuring the normal function of the Hh signaling pathway by directly or indirectly regulating each other's expression levels. And the interaction between Ihh and Gli1 significantly impacts the normal development of craniofacial tissues. This review summarizes the pivotal roles of Gli1 and Ihh in the intricate landscape of mammalian craniofacial development and outlines the molecular regulatory mechanisms and intricate interactions governing the growth of bone and cartilage exhibited by Gli1 and Ihh, which provides new insights into potential therapeutic strategies for related diseases or researches of tissue regeneration.

A Three-branch Jointed Feature and Topology Decoder guided by game-theoretic interactions for temporomandibular joint segmentation

Segmentation of the temporomandibular joint (TMJ) disc and condyle from magnetic resonance imaging (MRI) is a crucial task in TMJ internal derangement research. The automatic segmentation of the disc structure presents challenges due to its intricate and variable shapes, low contrast, and unclear boundaries. Existing TMJ segmentation methods often overlook spatial and channel information in features and neglect overall topological considerations, with few studies exploring the interaction between segmentation and topology preservation. To address these challenges, we propose a Three-Branch Jointed Feature and Topology Decoder (TFTD) for the segmentation of TMJ disc and condyle in MRI. This structure effectively preserves the topological information of the disc structure and enhances features. We introduce a cross-dimensional spatial and channel attention mechanism (SCIA) to enhance features. This mechanism captures spatial, channel, and cross-dimensional information of the decoded features, leading to improved segmentation performance. Moreover, we explore the interaction between topology preservation and segmentation from the perspective of game theory. Based on this interaction, we design the Joint Loss Function (JLF) to fully leverage the features of segmentation, topology preservation, and joint interaction branches. Results on the TMJ MRI dataset demonstrate the superior performance of our TFTD compared to existing methods.

MiR-708–5p deficiency involves the degeneration of mandibular condylar chondrocytes via the TLR4/NF-κB pathway

ObjectiveAgeing 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. MethodSZCs 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. ResultsBoth 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. ConclusionsAge-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. Data availabilityThe small RNA and mRNA sequencing data included in this study are available in the NCBI Gene Expression Omnibus (GEO) database (accession numbers GSE236980, GSE236977, and GSE 236978).

Transcriptomics analyses of IL-1β-stimulated rat chondrocytes in temporomandibular joint condyles and effect of platelet-rich plasma

The biological mechanism of action of platelet-rich plasma (PRP) in the treatment of temporomandibular joint (TMJ) osteoarthritis remains unclear. This study explored the mechanisms underlying interleukin (IL)-1β-induced inflammation and investigated the effect of PRP on TMJ condylar chondrocytes. Primary chondrocytes were isolated from the TMJ condyle of 4-week-old rats, and differentially expressed genes among three treatment groups (phosphate-buffered saline [control], IL-1β, and IL-1β + PRP) were identified using RNA-seq and characterized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes path-enrichment analyses. IL-1β caused inflammatory injury to chondrocytes by upregulating the TNF, NF-κB, and IL-17 signaling pathways and downregulating the MAPK and PI3K/Akt signaling pathways. PRP activated the MAPK and PI3K/Akt signaling pathways, exerting a protective effect on IL-1β-induced chondrocytes. PRP also activated the TNF and IL-17 signaling pathways, producing an inflammatory effect. Additionally, PRP increased the mRNA expression of the matrix catabolism-related genes Mmp3, Mmp9, and Mmp13; the proliferative markers Mki67 and PCNA; and the anti-apoptotic genes of the Bcl-2 family (Bcl2a1 and Bok), while reducing the expression of the pro-apoptotic genes Casp4 and Casp12. The findings suggest that the protective effect of PRP on IL-1β-induced chondrocyte injury is mainly achieved via MAPK-PI3K/Akt signaling, increasing cell proliferation and inhibiting cell apoptosis.

Osteoarthritis Disease Severity in the Temporomandibular Joint and the Knee Joint: A Comparative Cadaveric Study.

The objective of this study was to determine the level of disease severity in a pilot cohort of temporomandibular joints (TMJs) and compare them to the pathology findings previously characterized in cadaveric knee joints. Thirty-one intact TMJs from 17 cadaveric donors were harvested and arthritic lesioning seen in the knee joint was investigated on the condyle and the fossa of the TMJ. Prevalence of gross alterations was equated and disease severity was determined for sex- and age-based donor pools using a validated, osteoarthritis (OA) disease severity scale (DSS). Knee joint DSS scores were also compared to the TMJ condyle and fossa DSS scores and a case study was carried out on a male donor that demonstrated severe OA in the both joints. The mandibular fossa demonstrated an increase in disease severity compared to the mandibular condyle in a mixed sex donor pool (P = 0.035). It was discovered that the younger females demonstrated statistically more pathological condyles compared to the older half of the female subgroup (P = 0.02). TMJ fossa and knee joints demonstrated comparable OA severity and similar signs of cartilage disease in a single donor highlighting the systemic nature of OA. This study demonstrates that gross signs of OA in the TMJs of cadavers are comparable to pathology found in the knee. The mandibular fossa appears to be the site of more profound disease, implying translational movements may be more likely to induce biomechanically abnormal movement, loading, and OA.

Single-cell RNA sequencing analysis of the temporomandibular joint condyle in 3 and 4-month-old human embryos

BackgroundThe temporomandibular joint (TMJ) is a complex joint consisting of the condyle, the temporal articular surface, and the articular disc. Functions such as mastication, swallowing and articulation are accomplished by the movements of the TMJ. To date, the TMJ has been studied more extensively, but the types of TMJ cells, their differentiation, and their interrelationship during growth and development are still unclear and the study of the TMJ is limited. The aim of this study was to establish a molecular cellular atlas of the human embryonic temporomandibular joint condyle (TMJC) by single-cell RNA sequencing, which will contribute to understanding and solving clinical problems.ResultsHuman embryos at 3 and 4 months of age are an important stage of TMJC development. We performed a comprehensive transcriptome analysis of TMJC tissue from human embryos at 3 and 4 months of age using single-cell RNA sequencing. A total of 16,624 cells were captured and the gene expression profiles of 15 cell clusters in human embryonic TMJC were determined, including 14 known cell types and one previously unknown cell type, "transition state cells (TSCs)". Immunofluorescence assays confirmed that TSCs are not the same cell cluster as mesenchymal stem cells (MSCs). Pseudotime trajectory and RNA velocity analysis revealed that MSCs transformed into TSCs, which further differentiated into osteoblasts, hypertrophic chondrocytes and tenocytes. In addition, chondrocytes (CYTL1high + THBS1high) from secondary cartilage were detected only in 4-month-old human embryonic TMJC.ConclusionsOur study provides an atlas of differentiation stages of human embryonic TMJC tissue cells, which will contribute to an in-depth understanding of the pathophysiology of the TMJC tissue repair process and ultimately help to solve clinical problems.

Surgical Techniques and Functional Reconstruction for Complex Tenosynovial Giant Cell Tumor of Temporal Bone and Middle Skull Base.

Objectives: Temporal tenosynovial giant cell tumors (TGCTs) are often large and have invaded the middle skull base. It is difficult to protect the important neurovascular structures around the tumor and perform functional reconstruction on the basis of complete tumor resection. This study aimed at analyzing the surgical techniques and functional reconstruction during the operation of complex TGCT of temporal bone and middle skull base. Methods: Five patients with pathologically confirmed TGCT of different complex types in the temporal bone and middle skull base were treated in our hospital from December 2020 to February 2023. We collected and retrospectively analyzed their medical records, including medical imaging, surgical procedures, and follow-up data. Results: The tumors invaded beyond the temporal bone and destroyed the middle skull base in all cases, involving the intracranial space and other important neurovascular structures. The internal carotid artery, infratemporal fossa, pterygopalatine fossa, and parapharyngeal space were also involved in 1 case. All the patients' tumors were completely removed, and the operations were performed mainly via modified infratemporal fossa approach, or combined with expanded middle cranial fossa approach. All cases with temporal and skull base destruction were repaired using the temporalis muscle flap with no occurrence of intracranial complications. The dura mater, condyle of temporomandibular joint, facial nerve, and internal carotid artery were fully preserved. Normal maxillofacial morphology was also preserved. The air conductive hearing of 2 patients was preserved. Conclusions: We found and summarized some surgical techniques that can help safeguard the important structures around massive TGCTs of temporal bone and middle skull base, and reconstruct the defects after tumor resection. The techniques are effective and feasible.

Centric relation-A biological perspective of a technical concept.

Few terms and concepts have been so extensively debated in dentistry as the words 'centric relation' (CR). Debates involve its biological, diagnostic and therapeutic usefulness. A review of the literature on the current concepts on CR as a diagnostic or therapeutic aid in dentistry was provided. Clinical trials assessing the superiority of one CR recording method over the others to identify patients with temporomandibular disorders (diagnostic use) or to manage patients with prosthodontic or orthodontic needs (therapeutic use) were tentatively included. Due to the absence of literature addressing either of the above targets, a comprehensive overview was provided. The diagnostic use of CR as a reference position to identify the correct position of the temporomandibular joint condyle within the glenoid fossa is not supported and lacks anatomical support. From a therapeutic standpoint, the use of CR can be pragmatically useful in prosthodontics as a maxillo-mandibular reference position when occlusal re-organization is warranted and/or when the position of maximum intercuspation is no longer available. The derived occlusal goals from a diagnostic misuse of CR are generally the result of circular reasoning, that is a technique is based on the recording of a certain condylar position that is believed to be 'ideal' and the treatment is considered successful when such position is shown by the specific instrument that was manufactured for that purpose. The term 'Centric Relation' might be replaced with the term 'Maxillo-Mandibular Utility Position'.

Transcriptomic and proteomic studies of condylar ossification of the temporomandibular joint in porcine embryos.

The ossification mechanism of the temporomandibular joint (TMJ) condyle remains unclear in human embryo. The size and structure of TMJ, shape of articular disc and the characteristics of omnivorous chewing in the pig are similar to those of humans. The pig is an ideal animal for studying the mechanism of ossification of the TMJ condyle during the embryonic period. In a previous study by our group, it was found that there was no condylar ossification on embryonic day(E) 45, but the ossification of condyle occurred between E75 and E90. In this study, a total of 12 miniature pig embryos on E45 and E85 were used. Six embryos were used for tissue sections (3 in each group). The remaining six embryos were used for transcriptomic and proteomic studies to find differential genes and proteins. The differentially expressed genes in transcriptome and proteomic analysis were verified by QPCR. In total, 1592 differential genes comprising 1086 up-regulated genes and 506 down-regulated genes were screened for fold changes of ≥2 to ≤0.5 between E45 and E85. In the total of 4613 proteins detected by proteomic analysis, there were 419 differential proteins including 313 up-regulated proteins and 106 down-regulated proteins screened for fold changes of ≥2 to ≤0.5 between E45 and E85. A total of 36 differential genes differing in both transcriptome and proteome analysis were found. QPCR analysis showed that 14 of 15 selected genes were consistent with transcriptome analysis. Condylar transcriptome and proteomic analysis during the development of TMJ in miniature pigs revealed the regulatory genes/proteins of condylar ossification.

Association between chewing side preference and MRI characteristics in patients with anterior disc displacement of the temporomandibular joint

ObjectiveTo compare the magnetic resonance imaging (MRI) characteristics in the anterior disc displacement (ADD) patients with and without chewing side preference (CSP). MethodsThe MRI characteristics of the bilateral temporomandibular joint (TMJ) in 111 patients with ADD were retrospectively analysed. Based on the presence of CSP, all subjects were divided into the non-CSP group (NC group, N = 40) and CSP group (C group, N = 71). Based on the preferred chewing side in the C group, the patients were divided into ipsilateral and contralateral sides. The morphology, length, disc-condyle angle, and coordinate position of the disc and condyle of the bilateral TMJ were compared. ResultsMRI examination showed a significant difference between ipsilateral and contralateral joint displacement in patients with CSP (P<0.05). In CSP patients, the disc length of the same side in the ipsilateral side was significantly shorter than the contralateral side (P<0.05). A significant difference in the Y-axis coordinates of the ipsilateral and contralateral discs was also found in patients with CSP (P<0.05). The disc displacement grade, morphology of the articular disc, ipsilateral disc length, and ipsilateral disc-condyle Y-axis distance were positively correlated with CSP (P<0.05). ConclusionCSP is related to the shape of the articular disc and disc-condyle position in patients with ADD. CSP may aggravate the development of ADD.

Bulk RNA-seq analyses of mandibular condylar cartilage in a post-traumatic TMJ osteoarthritis rabbit model.

The temporomandibular joint (TMJ) is anatomically comprised of the mandibular condylar cartilage (CC) lined with fibrocartilaginous superficial zone and is crucial for eating and dental occlusion. TMJ osteoarthritis (OA) leads to pain, joint dysfunction and permanent loss of cartilage tissue. However, there are no drugs clinically available that ameliorate OA and little is known about global profiles of genes that contribute to TMJ OA. Furthermore, animal models that recapitulate the complexity of signalling pathways contributing to OA pathogenesis are crucial for designing novel biologics that thwart OA progression. We have previously developed a New Zealand white rabbit TMJ injury model that demonstrates CC degeneration. Here, we performed genome-wide profiling to identify new signalling pathways critical for cellular functions during OA pathology. Temporomandibular joint OA was surgically induced in New Zealand white rabbits. Three months following injury, we performed global gene expression profiling of the TMJ condyle. RNA samples from TMJ condyles were subjected to sequencing. After raw RNA-seq data were mapped to relevant genomes, differential expression was analysed with DESeq2. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted. Our study revealed multiple pathways altered during TMJ OA induction including the Wnt, Notch and PI3K-Akt signalling pathways. We demonstrate an animal model that recapitulates the complexity of the cues and signals underlying TMJ OA pathogenesis, which is essential for developing and testing novel pharmacologic agents to treat OA.

Evaluation of temporomandibular joint spaces and condylar position: A CBCT study

Temporomandibular joint (TMJ) is a unique joint. The dimension joint space is determined by the optimal Condylar position. Conventional radiographs cannot exactly show the relationship hence MRI and CT are being used frequently for imaging of TMJ. CBCT has recent advancement into technology especially in this field as helped to analyse the TMJ in more comphrehensive manner. The aim of this study is to assess the position of condyle in TMJ with patients of TMDs. The importance of relationship between condyle and glenoid fossa remains controversial. The CBCT utilizes less radiation and as higher resolution than normal CT. The position of condyle in the glenoid fossa is measured with high accuracy using CBCT technique for reconstruction and imaging of the TMJ. It provides reliable and accurate images. The study was designed to compare the condylar morphology in symptomatic and asymptomatic patients with TMD s.

Three-dimensional Assessment of Temporomandibular Joint Volume, and Condylar and Glenoid-fossa Morphology: A Cone-beam Computed Tomography Study.

The condylar and glenoid fossa morphology can alter in patients with temporomandibular disorders (TMD), which can lead to changes in the temporomandibular joint (TMJ) space volume. Volumetric evaluation of TMJ can represent the entire three-dimensional (3D)-joint space between the condyle and glenoid fossa. To perform 3D assessment of TMJ volume, condylar, and glenoid-fossa morphology using cone-beam computed tomography and evaluate the correlation between these parameters. Thirty-four patients (age: 13.50 years) who had no previous history of TMD were included. The volume of TMJ space was measured and divided into anterior, posterior, medial, and lateral TMJ volume. The antero-posterior (AP) and medio-lateral (ML) condylar width, AP and ML glenoid-fossa width, and glenoid-fossa depth were evaluated. Statistical analyses were performed with R software at a 0.05 significance level. Each parameter was compared between the left and right sides using a paired-t test. The correlations between the parameters were obtained by the Pearson correlation coefficient. There was no significant difference between lateral and medial TMJ volume; however, posterior TMJ volume was significantly greater than anterior TMJ volume. A significant correlation was observed between AP glenoid-fossa width and TMJ volume, glenoid-fossa depth and TMJ volume, AP position of the condyle and anterior TMJ volume, ML position of the condyle and medial TMJ volume, glenoid-fossa width and condyle width in AP and ML dimension, glenoid-fossa depth and AP glenoid-fossa width. In addition to the evaluation of condylar and glenoid-fossa morphology, assessment of TMJ space volume is important for comprehensive evaluation of the joint.

UNIFIED ALGORITHM OF REHABILITATION OF PATIENTS WITH OCCLUSIONAL DISORDERS OF IATROGENIC GENESIS COMBINED WITH VERTICAL MALOCCLUSION

Malocclusion is common dental diseases. According to epidemiological studies, occlusal pathology in the vertical plane is 5-7% among all anomalies. Occlusial problems contribute to the violation of basic body functions such as breathing, speech, chewing, which significantly impairs the quality of life of patients.Orthodontic treatment of adult patients has its own characteristics associated with the presence of concomitant pathology, as well as the inability to correct some pathologies only by orthodontic treatment. In the case of severe occlusion, complicated by tooth loss, a combination of surgical, orthodontic and prosthetic methods can achieve the best results. The key to successful treatment of such patients is a detailed diagnosis and a well-developed rehabilitation plan. Occlusive disorders, especially those that have arisen or been provoked as a result of dental treatment, usually lead to changes in all parts of the dental system and a number of complications. These structural changes usually make it difficult or sometimes impossible to conduct orthodontic treatment without the use of a set of special preparatory measures.&#x0D; The aim of our study: to propose a unified algorithm for complex dental rehabilitation of patients with occlusive disorders of iatrogenic origin in combination with vertical malocclusion and to prove its effectiveness.&#x0D; During 2019-2020, 55 patients with occlusive disorders of iatrogenic genesis in combination with pathology of occlusion in the vertical plane aged 23 to 47 years (mean age 36.1 ± 5.2 years) were examined, including 32 women and 23 men. Depending on the complaints and clinical manifestations, patients were divided into three groups. The first included 16 people with muscular manifestations, the second - 18 with disorders of the temporomandibular joint (TMJ) manifestations, the third - 21 people who, in addition to manifestations of TMJ and muscles, had primary neuritic disorders. All patients before and 6 months after treatment underwent clinical and laboratory examinations, radiography, electromyography and digital occlusion analysis of T-scan.&#x0D; There was a complete disappearance or significant reduction of complaints and symptoms after 6 months of rehabilitation in all 3 groups of patients. The implementation of our complex rehabilitation algorithm has led to the normalization of the bioelectrical activity of the masticatory muscles according to electromyography research, which is one of the most important criteria for the transition to the next stage of treatment and replacement of temporary restorations with permanent ones. Positive dynamics in the position of the TMJ condyles (tested with Computed Tomography) after the use of occlusal splints was observed in all patients and served as a marker for deciding to move to the next stage of dental treatment, including orthodontic correction. Also, occlusal balancing and normalization of the balance of occlusal contacts under the control of digital occlusal analysis T-Scan III was achieved in all patients in the preparatory stage and then monitored and maintained at all subsequent stages of comprehensive rehabilitation.&#x0D; Our study showed that the proposed algorithm for comprehensive rehabilitation of patients with iatrogenic occlusive disorders in combination with vertical malocclusion increases the effectiveness of orthodontic treatment of such patients and significantly reduces the duration of treatment in all 3 groups. This sequence of diagnostic and therapeutic measures provides the best opportunities for the patient to achieve maximum functional and aesthetic results.

Changes in Temporomandibular Joint Disc and Condyle after Rapid Maxillary Expansion Combined with Protraction Facemask Therapy: A Prospective Magnetic Resonance Imaging Study

Changes in Temporomandibular Joint Disc and Condyle after Rapid Maxillary Expansion Combined with Protraction Facemask Therapy: A Prospective Magnetic Resonance Imaging Study

Temporomandibular Joint Fibrocartilage Contains CD105 Positive Mouse Mesenchymal Stem/Progenitor Cells with Increased Chondrogenic Potential.

A specific type of mesenchymal stem/progenitor cells (MSPCs), CD105+ is reported to aid in cartilage regeneration through TGF-β/Smad2-signalling. The purpose of this study was to identify and characterize CD105+ MSPCs in temporomandibular joint (TMJ) cartilage. MSPCs were isolated from mouse TMJ condyle explants and evaluated for their clonogenicity and pluripotential abilities. MSPC were examined for CD105 antigen using immunohistochemistry and flow cytometry. Immunohistochemistry revealed presence of CD105+ MSPCs in the proliferative zone of condyle's cartilage. Only 0.2% of isolated MSPCs exhibited CD105, along with the stem cell surface markers CD44 and Sca-1. In CD105+ MSPCs, intracellular immunostaining revealed significantly higher (p < 0.05) protein levels of collagen type 1, 2, proteoglycan 4. Ability for chondrogenic differentiation was found to be significantly higher (p < 0.05) after 4weeks compared to CD105- cells, using alcian blue staining. CD105+ cells were found to resemble an early MSPC subgroup with significantly higher gene expression of biglycan, proteoglycan 4, collagen type 2, Gli2, Sox5 (p < 0.001) and Sox9 (p < 0.05). In contrast, significantly lower levels of Runx2 (p < 0.05), Osterix, Trps1, Col10a1 (p < 0.01), Ihh (p < 0.001) related to chondrocyte senescence and commitment to osteogenic lineage, were observed compared to CD105- cells. The study showed the existence of a CD105+ MSPC subgroup within TMJ fibrocartilage that may be activated to aid in fibrocartilage repair.

Novel roles of tendon in the postnatal growth and expansion of TMJ condyle

The Temporomandibular joint (TMJ) is one of the most complex joints in the human body. TMJ is composed of the temporal bone, a disc and a movable mandibular condyle with abundant tendon attachments. Tendon has been thought to play the sole function of transmitting muscle forces to stabilize joints, yet it is largely unclear why tendon undergoes ectopic ossification in trauma or diseases, and whether it has any direct contribution to skeletal formation. This study aimed to investigate the full biological significance of tendon in TMJ growth. We first discovered that the TMJ condyle is composed of a well‐established cartilage head and an overlooked “bony head” that grows after birth and continuously expands throughout the lifespan with little signs of remodeling. Mouse X‐ray images (Fig.1a) showed little change in the cartilage head’s volume but a continuous expansion in the bony head’s mass with a low mineral content from 1 to 5 months (Fig.1b). Toluidine blue staining showed TMJ condyle had a large area of tendon attachment extending down to ramus (Fig.1c, white dotted line in lower magnification), defined by regions of tendon, interface, and TFB (Fig.1c1). The TFB morphology was distinct from endosteum‐formed bone (EFB, Fig.1c1), cartilage‐formed bone (CFB, Fig.1c2, rich in cartilage residual), or periosteum‐formed bone (PFB, Fig.1c3) in cell shape and distribution, and ECM. TEM images further revealed that the osteocytes in the TFB were large in size, irregular in shape, had small nuclei but numerous ERs and Golgi complexes, and were embedded in ECM rich in fibropositors. In contrast, the osteocytes in EFB, CFB or PFB were spindle‐shaped with larger nuclei but fewer ERs and Golgi complexes (Fig.1d). To reveal the cell source of the bony head, cell lineage tracing were used. Tracing data showed that most CFB cells originate from Col10a1+ hypertrophic chondrocytes, whereas the interface and TFB were derived from Scx+ cells (Fig.1e). RNAscope displayed high levels of Thbs4 (Thrombospondin‐4, a tendon marker) and SOST (a potent inhibitor of Wnt signaling secreted by osteocytes) mRNA in TFB at bony head (Fig.1f). The Scx‐CreERT2 tracing combined with IHC staining showed TFB maintained a mixed ECM of bone (Col1), cartilage (Aggrecan) and tendon (Periostin, Fig.1g). To further determine the role of tendon lineage in condyle expansion, we generated Scx‐CreERT2; R26RDTA (carrying a loxP‐flanked stop cassette associated with an attenuated diphtheria toxin fragment A, DTA, for the ablation of cells when Cre is active). Deletion of Scx+ cells greatly reduced the size of bony head (Fig.1h) and the thickness of interface with few Scx+/Col1+ bone cells in P28 DTA mice (Fig.1i); In conclusion, our study tendon cells, beyond their conventional role in joint movement, are key players for the postnatal growth and expansion of TMJ condyle (Fig.1j).

Multimodal imaging analysis of the cyst like lesion of condyle in temporomandibular joint

Objective: To investigate the imaging features of condylar cystic degeneration of temporomandibular joint (TMJ) by cone-beam CT (CBCT), spiral CT, MRI and radionuclide bone imaging. Methods: From January 2018 to December 2020, thirty-two patients with cyst-like lesions of condylein temporomandibular joint were examined by CBCT, spiral CT, MRI and radionuclide bone imaging at the Department of Oral and Maxillofacial Surgery in General Hospital of Chinese PLA. There were 12 males and 20 females involved, aged from 16 to 65 years with an average age of (33.9±12.5) years. The characteristics of CBCT, spiral CT, MRI and radionuclide bone imaging were analyzed. Condylar cyst like lesions were classified as type A and type B based on the presence or absence of surface bone defects. Condylar cyst like lesions were classified as type Ⅰ(yes) and type Ⅱ(no) according to the accompanying bone marrow edema-like lesions of the condyles. The incidence of condylar bone marrow edema, disc displacement and abnormal bone metabolism were analyzed. Results: A total of 64 joint images of 32 patients were included, including 34 sides with TMJ cyst-like lesion and 6 sides with multiple cyst-like lesions,the total cyst-like lesions were 42. The largest diameter of cyst-like lesion ranged from 1.0 to 12.4 mm, with an average length of (3.7± 1.8) mm. There were 24 cases of type A TMJ cyst like lesion and 10 cases of type B cyst-like lesion. The detection rate of CBCT was 95.2% (40/42) and that of spiral CT was 100% (42/42), there was no significant difference (Calibration Chi-square=0.51, P=0.474). The detection rate of nuclear magnetic resonance was 80.1% (34/42), and the detection rate of cyst-like lesions less than 2 mm was 3/11. In the cyst like lesion side, there were 9 sides with anterior disc displacement with reduction, 20 sides with anterior disc displacement without reduction. In the non-cyst like lesion side, 10 sides with anterior disc displacement with reduction and 6 sides with anterior disc displacement without reduction. There was a significant difference in the displacement of the disc between cyst-like and non-cystic lesion side (χ²=7.80, P=0.005). MRI showed that 6 cases of cystic side[17.6% (6/34)] had bone marrow edema-like lesions (all type A), 1 case of non-cyst like lesions side [3.3% (1/30)] had bone marrow edema-like lesion, there was no significant difference between cystic and non-cystic lesions (Calibration Chi-square=2.04, P=0.153). There was a significant difference between type A and B cystic lesions (Fisher exact probability method, P=0.024). Radionuclide bone imaging showed abnormal bone metabolism in 26 patients in the cyst-like lesion side and 5 patients in the non-cyst like lesion side (χ²=22.82, P<0.001). Conclusions Multi-slice Spiral CT could detect the cyst-like lesion of TMJ condyle in the early stage, which is different from the large joint. And the formation mechanism may vary from the different classifications.

Multimodal imaging analysis of the cyst like lesion of condyle in temporomandibular joint

Objective: To investigate the imaging features of condylar cystic degeneration of temporomandibular joint (TMJ) by cone-beam CT (CBCT), spiral CT, MRI and radionuclide bone imaging. Methods: From January 2018 to December 2020, thirty-two patients with cyst-like lesions of condylein temporomandibular joint were examined by CBCT, spiral CT, MRI and radionuclide bone imaging at the Department of Oral and Maxillofacial Surgery in General Hospital of Chinese PLA. There were 12 males and 20 females involved, aged from 16 to 65 years with an average age of (33.9±12.5) years. The characteristics of CBCT, spiral CT, MRI and radionuclide bone imaging were analyzed. Condylar cyst like lesions were classified as type A and type B based on the presence or absence of surface bone defects. Condylar cyst like lesions were classified as type Ⅰ(yes) and type Ⅱ(no) according to the accompanying bone marrow edema-like lesions of the condyles. The incidence of condylar bone marrow edema, disc displacement and abnormal bone metabolism were analyzed. Results: A total of 64 joint images of 32 patients were included, including 34 sides with TMJ cyst-like lesion and 6 sides with multiple cyst-like lesions,the total cyst-like lesions were 42. The largest diameter of cyst-like lesion ranged from 1.0 to 12.4 mm, with an average length of (3.7±1.8) mm. There were 24 cases of type A TMJ cyst like lesion and 10 cases of type B cyst-like lesion. The detection rate of CBCT was 95.2% (40/42) and that of spiral CT was 100% (42/42), there was no significant difference (Calibration Chi-square=0.51, P=0.474). The detection rate of nuclear magnetic resonance was 80.1% (34/42), and the detection rate of cyst-like lesions less than 2 mm was 3/11. In the cyst like lesion side, there were 9 sides with anterior disc displacement with reduction, 20 sides with anterior disc displacement without reduction. In the non-cyst like lesion side, 10 sides with anterior disc displacement with reduction and 6 sides with anterior disc displacement without reduction. There was a significant difference in the displacement of the disc between cyst-like and non-cystic lesion side (χ²=7.80, P=0.005). MRI showed that 6 cases of cystic side[17.6% (6/34)] had bone marrow edema-like lesions (all type A), 1 case of non-cyst like lesions side [3.3% (1/30)]had bone marrow edema-like lesion, there was no significant difference between cystic and non-cystic lesions (Calibration Chi-square=2.04, P=0.153). There was a significant difference between type A and B cystic lesions (Fisher exact probability method, P= 0.024). Radionuclide bone imaging showed abnormal bone metabolism in 26 patients in the cyst-like lesion side and 5 patients in the non-cyst like lesion side (χ²=22.82, P<0.001). Conclusions Multi-slice Spiral CT could detect the cyst-like lesion of TMJ condyle in the early stage, which is different from the large joint. And the formation mechanism may vary from the different classifications.