Condylar Cartilage Research Articles

Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.

Development of the blood supply to the growth cartilage of the medial femoral condyle of foals.

Growth cartilage is found in the articular-epiphyseal cartilage complex (AECC) and the physis. It has a temporary blood supply organised as end arteries. Vascular failure is associated with osteochondrosis, but infection can also obstruct vessels. The location of bacteria was recently compared to arterial perfusion, and the results indicated that they were located in the distal tips of AECC end arteries. Systematic perfusion studies were not available for comparison to the infected physes. Further studies may improve our understanding of infections and other pathologies. To describe development of the blood supply to the growth cartilage of the medial femoral condyle in fetuses and foals from 228days of gestation to 62days old. Ex vivo arterial perfusion study. The left medial femoral condyle of 10 Norwegian Fjord Pony fetuses and foals (228days of gestation to 62days old) and one Norwegian-Swedish Coldblooded Trotter foal (10days old) was arterially perfused with barium and underwent micro-computed tomography, qualitative and quantitative description of vessels. In the fetus, the physis was supplied by metaphyseal-origin arteries. In 1-10day-old foals, the physis was supplied by a mixture of metaphyseal- and epiphyseal-origin arteries, and from 15 days of age by epiphyseal-origin arteries only. The number of vessels increased before it decreased in both the AECC and the physis postnatally. Vessels in the cartilage showed a monopodial branching pattern, whereas vessels in epiphyseal and metaphyseal bone showed both monopodial and dichotomous branching. Foals with confirmed pathologies were not examined. The blood supply to growth cartilage changed with age, including the physeal supply that changed from metaphyseal- to epiphyseal-origin arteries. The number of vessels increased before it decreased postnatally, and two different branching patterns were observed. These results may improve our understanding of growth cartilage vascular failure and osteomyelitis.

Histomorphometric Evaluation of the Effects of Mandibular Advancement Appliance and Low Level Laser Therapy (LLLT) with Different Doses on Condylar Cartilage and Subchondral Bone in Rats

Histomorphometric Evaluation of the Effects of Mandibular Advancement Appliance and Low Level Laser Therapy (LLLT) with Different Doses on Condylar Cartilage and Subchondral Bone in Rats

Effect of Simvastatin on Iodoacetate-induced Temporomandibular Joint Osteoarthritis in Rats

Objectives: osteoarthritis (OA) is one of the harmful disorders affecting the body joint including the temporomandibular joint (TMJ). Although OA is believed to be non-inflammatory disorder, antiinflammatory agents, as simvastatin, have been used for OA treatment. Simvastatin is presumed to possess antiosteoarthritic effect beside its antilipidemic influences. The present study tried to estimate the effect of simvastatin on the monoiodoacetate (MIA)-induced TMJ osteoarthritis. Materials and methods: thirty young adult female Sprague-Dawley rats were randomly categorized into; control, osteoarthritis and osteoarthritis with simvastatin groups. Both MIA for osteoarthritis induction and simvastatin for therapy were delivered unilaterally via the intra-articular route at the right side as a single dose for each. Results: the simvastatin administration has relatively reduced the MIA-induced osteoarthritic manifestations, and/or inhibited the progress of some osteoarthritic degenerative features but it failed to control others. The most striking findings with simvastatin administration were the prominent thickening of the condylar proliferative layer, as well as the development of osteophytes at the anterior pole of mandibular condyle. The condylar cartilage matrix showed enhancement of the extracellular matrix production with simvastatin administration. Discussion: the present study has clarified the relative antiosteoarthritic effect of simvastatin intraarticular injection. Though simvastatin has valuable palliative effect, it failed to prevent the advancement of some osteoarthritic manifestations. Conclusion: temporomandibular joint osteoarthritis (TMJOA) treated by simvastatin relieve some osteoarthritic features and modulate the structure of some joint components to compensate the damaged induced structures with MIA.

Cartilage articulation enhances chondrocyte injury and death after impact injury

Purpose: Post-traumatic osteoarthritis results from physical trauma to joints due to cartilage damage and inflammation. Adverse biological responses include mitochondria (MT) depolarization which occurs minutes after injury, leading to bioenergetic failure of the cell through decreased ATP production. MT depolarization also leads to caspase activation and excess reactive oxygen species production, resulting in apoptosis and cell death respectively. Previous work has shown that both impact injury and sliding cause cellular damage in healthy cartilage tissue, however it is unknown if damage would be exacerbated by impacting and then sliding injured cartilage. These combined mechanical forces would more closely simulate the mechanical environment of an injured joint that is subject to continued use after trauma. We hypothesize that sliding injured tissue leads to increased chondrocyte damage throughout the depth of the tissue. Methods: Femoral condyle cartilage of 6 neonatal bovids was collected within 24 h of sacrifice and sectioned into cylindrical plugs (6 mm diameter by 2 mm thick), using sterile practices, and incubated overnight prior to impact. Cartilage plugs were randomly assigned to one of 4 treatment groups (n ≥ 7/group): uninjured control, impact, sliding, or impact followed by sliding. A cylindrical indenter was used to impact cartilage plugs in unconfined axial compression (2.36 ± 0.31 MJ/m3). Impacts were characterized at 50 kHz using a load cell and linear variable differential transducer to measure impact force and cartilage deformation. A custom tribometer was used to slide samples at 1 mm/s for 1 h. Samples were compressed to 15% axial strain and submerged in a lubricating bath of bovine synovial fluid. Samples were axially bisected after injury, stained for either chondrocyte viability (Calcein AM and ethidium homodimer), apoptosis (CellEvent Caspase-3/7 Green), or MT polarization (MitoTracker Green and tetramethylrhodamine). The cross-section (550 μm x 725 μm) was imaged using confocal microscopy at a minimum of 3 h after injury. Bulk tissue and depth-dependent cellular response was quantified using confocal images and a custom MATLAB code. Statistical analysis was conducted using a two-way ANOVA with significance evaluated at p &lt 0.05 for both bulk tissue and depth-dependent results. Results: Bulk tissue analysis revealed that individually, impact and sliding caused increased chondrocyte death and damage for all assessments, with impact having the greater effect, however the combination further increased cell damage and death (Figure 1A-C). For cell death and apoptosis, the effects of impact and sliding were additive, while for MT depolarization the effect was more than additive (Figure 1C) (p = 0.016 for interaction via two-way ANOVA). Examining the spatial patterns of chondrocyte damage and death (Figure 2A-C) revealed that all treatments resulted in cell damage and death that was highest near the articular surface and decreased with depth from the surface. In controls cell death, apoptosis, and MT depolarization were unaffected deeper in the tissue. Sliding alone resulted in levels of cell death, apoptosis, and MT depolarization that were not different from controls deeper into the tissue (p &gt 0.05). Impact alone increased cell death, and MT depolarization in the deeper regions of the cartilage compared to controls (p &lt 0.05). The combination of impact and sliding was nominally higher than either impact or sliding alone, but the interaction was only statistically higher for MT depolarization (Figure 2C). This combination resulted in dramatically higher MT depolarization deeper in the tissue compared to the impact only group (∼60% vs ∼30%, p = 0.005). Conclusions: The goal of this study was to assess the combined effects of two types of loading experienced in joints after trauma. The data show that both impact injury and sliding affect chondrocyte damage. Damage was primarily concentrated at the articular surface, which indicates the surface acts as a protective layer to limit damage propagation deeper into the tissue. Assessments of cell death and apoptosis show additive effects of the combination treatment. However, this combination causes synergistic damage in the assessment of MT depolarization, particularly deeper in the tissue. This population of cells with MT depolarization represents a possible mechanism by which damage propagates to other areas of the tissue and joint. As such this cell population represents a potential target for therapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Clinical and morphological features of age-related, posttraumatic and metabolic phenotypes of late stage knee osteoarthritis

Purpose: To verify clinical, functional, and morphological differences among age-related, posttraumatic and metabolic osteoarthritis (OA) phenotypes in patients with advanced gonarthrosis. Methods: The study covered 120 patients with gonarthrosis (Altman R.D., 1991) of III-IV radiological stages (Kellgren and Lawrence, 1957) hospitalized for total knee replacement. Age-related (over 50 years, absence of previous joint injury and metabolic syndrome, normal body mass index), posttraumatic, metabolic, mixed phenotypes (combination of all factors) were identified and studied, taking into account influence of the most common OA risk factors and proposed classifications in scientific literature (G.Musumeci et al., 2015; A.Dell'Isola et al., 2016; G.Herrero-Beaumont et al., 2017). There were 30 people in every group, and the informed consent was obtained. All patients have undergone clinical examination with filling out WOMAC questionnaire, algofunctional Lequesne index for knee OA, Visual Analogue Scale (VAS). To assess the quality of life the questionnaire MOS SF-36 was used. In 10 patients of every group (total n=40), histopathological study of medial tibiofemoral condyle cartilage and areolar synovial membrane of knee joints was performed using histochemical methods, Mankin H.J.(1971) and Krenn V.(2002) scales. Quantitative data were processed statistically. Results: Female predominance was found in all groups, however the largest number of women was found in metabolic (n=26, 86.7%) and mixed (n=26, 86.7%) phenotypes in comparison with age-related OA (n=18, 60%; р=0,019). The average age of patients with age-related phenotype was the highest (72,5[63; 77] years), and significant differences were detected compared with posttraumatic (62,5 [59; 64] years, p=0.001), metabolic (63 [57;68] years, p = 0.010), mixed (60 [56;64] years, p=0.001) OA. Synovitis was revealed significantly more frequently in metabolic OA (n=23, 76.7%) in comparison with age-related phenotype (n=13, 43.3%; р=0.008). The pain level according to VAS corresponded to severe (7-8 points) in all patients and did not have significant differences between the groups. The highest values of WOMAC questionnaire were found in metabolic phenotype (188 [162;207]), the lowest - in posttraumatic OA (129 [100;166], р=0,001). Lequesne index was the lowest in patients with posttraumatic phenotype (15 [14;19]) and the highest in patients with age-related and metabolic OA (20 [18;21], р=0,004; 20 [19;23], р=0,003, respectively). The lowest values of quality of life were in group of patients with metabolic phenotype (Physical Health - 28 [24.3;31.9], Mental Health - 30.9 [26.9;35.9]), the highest - in posttraumatic OA (34,1 [30,5;36,1], р=0,014 and 40,4 [32,9;43,8], р=0,005, respectively). Histopathological study showed that articular cartilage of patients with age-related OA phenotype was characterized by deep erosions, denudation of subchondral bone, hypocellularity, severe decrease of proteoglycans content. In synovial membrane, lipomatosis and severe inflammatory infiltration were found. In posttraumatic OA numerous surface defects, fibrous cartilage replacement, and chondrocyte clustering were revealed in articular cartilage, and fibrosis was detected in synovial membrane. In metabolic phenotype pronounced vascularization, ossification of articular cartilage, synovial hyperplasia, microcirculation disorders and monocyte/macrophage infiltration were observed. Mixed OA was characterized by combination of variable sings. The most severe cartilage damage according to Mankin scale was shown in age-related OA (8.5 [6;10] points). Significant differences were found in comparison with metabolic phenotype (6 [4.5;6.5] points; (р=0,001). High-grade synovitis was detected in patients with age-related and metabolic OA (5 [3;8] and 4 [3;5] points by Krenn scale, respectively). Conclusions: Age-related, posttraumatic and metabolic OA phenotypes in patients with III-IV radiological stages of gonarthrosis are characterized by various clinical and morphological features. In age-related OA phenotype late clinical debut, moderate pain and dysfunction of knee joints, severe degenerative-dystrophic changes in cartilage and synovial membrane were observed. Posttraumatic OA phenotype was characterized by mild clinical and functional disorders, acceptable quality of life of patients, severe cartilage damage, activation of reparative mechanisms, synovial fibrosis. In metabolic OA phenotype female predominance, frequent clinical synovitis, pronounced clinical and functional manifestations, low quality of patients life, cartilage vascularization and ossification, severe synovial microcirculation disorders were found. Mixed OA phenotype was characterized by variable clinical and morphological picture.

Hyaluronic acid-based shape memory cryogel scaffolds for focal cartilage defect repair

Purpose: Traumatic joint injuries can result in focal cartilage defects that regenerate poorly due to a lack of blood supply and low chondrocyte density. Cell-laden hydrogel scaffolds are under study but provide little flexibility in modulating their pore size, interconnectivity, swelling and stiffness, properties required for a conducive biomimetic environment. In this study, we engineered an injectable and biomimetic shape memory hyaluronic acid (HA)-based cryogel scaffolds with a macroporous and highly interconnected network in three-dimensions seeded with chondrocytes. Due to their unique ability to withstand up to 90% strains and rapidly recover their shape back, they can be arthroscopically delivered to fill up focal chondral defects for cartilage repair. Here we studied whether chondrocytes encapsulated within cryogels remain viable and metabolically active following injection and provide a superior micro-environment than conventional (nanoporous) hydrogels for cartilage regeneration. We also investigated how RGD-functionalized cryogel affects chondrocyte adhesion, migration and proliferation. Methods: Synthesis of HA-based Cryogels and Hydrogels: HA cryogels were prepared using HA modified with glycidyl methacrylate (HAGM) and either Acryl-PEG-G4RGDS to synthesis gels functionalized with RGD (Cryo RGD+) or Acryl-PEG-methoxy to synthesize gels without RGD (Cryo RGD-) in deionized (DI) water. The mixture was cast in 6 mm diam x 1.5 mm cylindrical discs using APS/TEMED as our initiator system. The samples were frozen at -20°C and allowed to cryopolymerize overnight. Next, cryogels were brought to RT and washed/sanitized prior to cell seeding. HA hydrogels (Hydro RGD+) were fabricated via photopolymerization by mixing HAGM, RGD, and lithium phenyl-2,4,6- trimethylbenzoylphosphinate (LAP) photo-initiator in DI water. Chondrocyte seeding and in-vitro culture:Chondrocytes harvested from calf knee femoral condyle cartilage were seeded onto each scaffold and cultured for 15 days. Injectability test: Cell-laden cryogels were incubated overnight to enable complete cell adhesion and subsequently syringe injected through a 16-gauge needle before incubation for another 24h following which cell viability and metabolism were quantified. Biochemical analysis: At the end of 15-day culture, gel samples were digested to quantify the cell metabolism (Alamar Blue), DNA (PicoGreen) and GAG (DMMB) content. Cell viability and cytoskeleton staining: Gel samples were fixed and stained for nucleus, actin, dead cells and confocal imaged at 40x. Results: Shape memory HA-based cryogels fully recovered their shape back following syringe injection through a 16-gauge needle without impacting cell metabolism or viability (Figs 1A-C). Scanning electron microscopy (SEM) images showed an average pore size of 49.2 ± 15 μm (Fig 1D) rendering a macroporous structure with high interconnectivity, which was 7x higher than hydrogels (Fig 1E). This unique macrostructural architecture enables efficient transport of nutrients and metabolites thereby offering a superior microenvironment for chondrocytes; both cell metabolism and GAG content was 2x higher in cryogels than hydrogels after 15-day culture (Figs 1F-G). Additionally, a significant amount of GAG (∼70 μg) was released from both cryogels into media owing to their macroporous structure; no released GAG was measured in media from Hydro RGD+ (Fig 1G). The presence of RGD (cell-adhesion peptide) did not improve cell adhesion or biosynthesis rates. Chondrocytes formed larger organoid-like structures in Cryo RGD- while remaining homogenously dispersed in the presence of RGD in Cryo RGD+ (Fig 1H). Conclusions: Syringe injectable HA-based shape memory cryogels provide a conducive microenvironment for chondrocyte adhesion, proliferation and matrix biosynthesis for use in repair of cartilage defects.

Indian hedgehog in craniofacial neural crest cells links to skeletal malocclusion by regulating associated cartilage formation and gene expression.

The frontal craniofacial skeleton derived from neural crest cells is vital for facial structure and masticatory functions. The exact role of Indian hedgehog (Ihh) in facial and masticatory development has not been fully explored. In this study, we generated craniofacial neural crest cells-specific Ihh deletion mice (Wnt1-Cre;Ihhfl/fl ;Tomatofl/+ ) and found the gradual dwarfism without perinatal lethality. Morphological and histological analyses revealed unambiguous craniofacial phenotypes in mutants, where we observed skeletal malocclusion accompanied by markedly hypoplastic nasomaxillary complex and reversed incisor occlusion. Both the replacement of nasal concha cartilage by turbinate bones and the endochondral ossification of nasal septum ethmoid bone were substantially delayed. We also observed hypoplastic mandibles in mutants where the mandibular ramus was unexpectedly the most affected. Both the condylar process and mandibular angle cartilages were distorted. However, dental examination showed no significant changes in teeth and dentition. Finally, a comprehensive RNA sequence analysis utilizing condylar cartilage identified Ihh-associated gene network including several cell cycle genes and 16 genes related to the extracellular matrix, sulfate transporters, transcription factors, receptors, a ciliogenesis factor, and an adhesion molecule. Our data provide direct in vivo evidence that Ihh plays crucial roles in midface and masticatory system formation, likely by activating key genes.

Comparison between two rabbit models of posttraumatic osteoarthritis: A longitudinal tear in the medial meniscus and anterior cruciate ligament transection

Animal osteoarthritis (OA) models have been developed to understand OA progression and evaluate new OA therapies. However, individual variations in joint lesions remain a critical problem in most current OA models. We established a novel rabbit model by creating a longitudinal tear in the medial meniscus body that was reproducible and similar to posttraumatic biomechanical disturbances in human OA. New Zealand rabbits underwent surgery and were assessed for 9 weeks. The rabbits were randomized into the sham control, medial meniscal tear (MMT), and anterior cruciate ligament transection (ACLT) groups. The animals were sacrificed at 4, 6, and 9 weeks posttreatment. The knee joints were harvested for histological and gene expression assessments. Both the MMT and ACLT procedures led to time-dependent degenerative changes in the femoral condyle cartilage. At each time point, the MMT group cartilage showed more severe degenerative changes than did the ACLT group cartilage. Consistently, inflammatory cytokine and catabolic gene expression were significantly higher, and anabolic gene expression was significantly lower in the MMT group than in the ACLT group. MMT treatment caused more severe structural damage to the cartilage and higher catabolic gene expression levels than the ACLT model at each time point. The MMT model may be highly beneficial in investigating posttraumatic OA (PTOA) development, especially PTOA from a meniscal injury. The MMT model replicated key features of human PTOA, including meniscal lesions, inflammatory responses, and the progression to osteoarthritic cartilage degeneration, thereby providing an exciting new avenue for translating promising treatments to clinical practice.

Identification of human temporomandibular joint fibrocartilage stem cells with distinct chondrogenic capacity

This study was aimed to identify the residence of human fibrocartilage stem cells (hFCSCs), characterize their stem cell properties and investigate the functional mechanisms which regulate fibrocartilage stem cells (FCSCs) toward chondrogenic differentiation during cartilage homeostasis and repairing. Cytological characteristics of hFCSCs and human orofacial mesenchymal stem cells (hOFMSCs) were analyzed. Chondrogenic potential of hFCSCs was compared with hOFMSCs both in vitro and in vivo. Regulatory role of SOX9 during FCSCs chondrogenesis was studied by shRNA interference in vitro, and by GFP+ FCSCs treatment in rat condylar cartilage defect model. SOX9 expression was also examined in temporomandibular joint osteoarthritis (TMJOA) patients' cartilage surface. hFCSCs exhibited typical mesenchymal stem cell characteristics, with significantly stronger chondrogenic capability compared to hOFMSCs. Moreover, hFCSCs showed remarkably increased expression of SOX9. During cartilage pellet culture, there was stronger SOX9 expression in hFCSCs than hOFMSCs. SOX9 shRNA interference downregulated chondrogenic capability of hFCSCs in vitro, as well as disrupting migration and chondrogenic differentiation of GFP+ FCSCs toward mature chondrocytes in rat condylar cartilage defect. Of note, SOX9 expression was also found suppressed in the condylar superficial zone of TMJOA patients. We found the existence of FCSCs in human TMJ cartilage, and characterized their distinct stem cell features. SOX9 is essential for hFCSCs chondrogenic differentiation, and a comprehensive understanding of the regulatory role of SOX9 in hFCSCs would be important for exploring potential intervention strategy of condylar cartilage degradation during TMJ disorders.

Effect of functional lateral shift of the mandible on hyaluronic acid metabolism related to lubrication of temporomandibular joint in growing rats.

Hyaluronic acid (HA) is a major molecular component of the articular cartilage of the temporomandibular joint (TMJ) influencing joint lubrication. Functional lateral shift of the mandible (FLSM) can lead to malocclusion. This study investigated the effects of FLSM on HA metabolism and lubrication of the TMJ in growing rats. Thirty 5-week-old male Wistar rats were divided into shift, recovery, and control groups. Rats in the shift and recovery groups were fitted with guiding plates to produce a 2-mm FLSM which were removed from the rats in the recovery group 14 days later. Animals were sacrificed at 14 and 28 days after the appliances were attached. Immunohistochemistry of HA-binding protein (HABP), hyaluronan synthase (HAS), and hyaluronoglucosaminidases (HYALs) was examined. The thickness of HABP-positively stained areas in the lateral regions in the bilateral condyle was reduced during the experimental period in the shift group compared with that in the control group. The proportion of HAS2-stained areas was bilaterally decreased in different regions of condylar cartilage during the experimental period in the shift group. The reduction of the HYAL2-stained area proportion in the condylar cartilage was more significant than that of HYAL1 at 14 days after appliance attachment in the shift group. HAS2 staining was not recovered in the recovery group. This research was based on animal experiments with a limited experimental period. FLSM altered lubrication related HA metabolism in the articular cartilage of the TMJ in growing rats.

Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis.

Exosomes are nanosized vesicles (30–140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration.

The effect of celecoxib in traumatic heterotopic ossification around temporomandibular joint in mice

In this study, the role of inflammation in traumatic heterotopic ossification around temporomandibular joint (THO-TMJ), as well as the preventive and treatment effect of celecoxib in THO-TMJ both in vivo and in vitro were explored. A surgically-induced THO-TMJ mouse model and a co-culture model of ATDC-5 or MC3T3-E1 and RAW-264.7cells were used in this study for in vivo and in vitro research. A series of inflammatory factors, such as CD3, CD68, CD20, IL-10, IL-6 and TNF-α, were activated 48h after trauma in a THO-TMJ model. Local trauma initiated systemic inflammatory responses as well as T cell- and macrophage-mediated local inflammatory responses around TMJ. In addition, expression of COX-2 was significantly elevated. The findings also showed that local injection of celecoxib could effectively alleviate the inflammatory response around TMJ at the early stage of trauma and inhibit the formation of THO-TMJ in vivo. Meanwhile, celecoxib could inhibit chondrogenic differentiation of ATDC-5 and osteogenic differentiation of MC3T3-E1 under inflammatory condition in vitro. Furthermore, celecoxib could inhibit the expression of Bmpr1b in the injured condylar cartilage at the initiation stage of THO-TMJ, which implied that Bmpr1b expressed by the residual condylar cartilage might be related to the pathogenesis of THO-TMJ. Inflammation played a crucial role in the pathogenesis of THO-TMJ, and anti-inflammation might be a possible choice to inhibit THO-TMJ, which provided scientific clues for the mechanisms, pharmacotherapy and molecular intervention of THO-TMJ.

Mechanoresponsive and lubricating changes of mandibular condylar cartilage associated with mandibular lateral shift and recovery in the growing rat.

The in vivo mechanoresponsive and lubricating changes of the mandibular condylar cartilage (MCC) associated with mandibular lateral shift (MLS) and recovery are poorly understood. Using growing rats, we investigated whether the expression of mechanoresponsive factors, including proteoglycan-4 (PRG4), Indian hedgehog (Ihh) and transforming growth factor-β1 (TGF-β1), would be affected by MLS. We also investigated whether these changes could recover to the control level after a 2-week treatment reversal (TR). The MLS appliances were placed for 2 or 4weeks in 5-week-old rats and removed from 7-week-old rats in the TR group. The MCC was analysed histomorphometrically by toluidine blue staining. Reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the expression of PRG4, Ihh, PTHrP (parathyroid hormone-related protein), TGF-β1, Matrix metallopeptidase 13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). A thickened superficial layer and an enhanced expression of PRG4 were detected in MLS groups. PTHrP-Ihh expression correlated positively with the up-regulation of PRG4. TGF-β1 expression decreased in the early stage of MLS but recovered to the control level in the TR group. A significantly enhanced expression of MMP-13 in MLS groups was detected. MLS treatment, which acted on the growth stage of rats, affected the morphology and expression of lubrication factor in the MCC. Elimination of this mechanical stimulus may help MCC recover to normal conditions. Our study supports that the adaptive changes of MCC, which are caused by mandibular functional deviation, could be largely recovered by early treatment.

Early efficacy of lateral unicondylar replacement for lateral compartment osteoarthritis of the knee

Objective: To discuss the surgical technique of lateral unicondylar knee replacement (UKR) for patients with lateral compartment osteoarthritis and evaluate its recent clinical efficacy. Methods: A retrospective analysis was conducted on 22 cases of lateral compartment osteoarthritis patients receiving lateral UKR at Orthopedic Department, Beijing Chao Yang Hospital, Capital Medical University from January 2016 to January 2019.There were 8 males (8 knees) and 14 females (14 knees), aged 65.7 years(range: 54 to 83 years). All patients completed preoperative imaging examination and excluded extra-articular deformity. Lateral parapelatellar approach was used for the operation and the tibial osteotomy was performed by extramedullary positioning.The residual cartilage of the external condyle was removed by pendulum saw to subchondral bone.Appropriate prosthesis were selected, and the tightness of the gap and the stability of the joints were repeatedly confirmed during the operation. The postoperative complications and the results of physical and imaging examinations were collected. The preoperative and postoperative Oxford knee Score (OKS) and knee society score (KSS) of patients were recorded and compared by paired t test. Results: All patients were followed up for 24.6 months (range: 8 to 40 months). No complications such as incision exudation, skin necrosis and deep venous thrombosis of lower limbs were found after the operation.No cases of prosthesis loosening, excessive wear of pads, dislocation and postoperative infection were found at the last follow-up.The OKS decreased from 46.5±3.1 preoperative to 22.4±3.3 postoperative(t=13.4, P=0.00) and KSS improved from 69.5±8.7 preoperative to 90.2±7.4 postoperative (t=16.9, P=0.00). Conclusions: For the treatment of lateral compartment osteoarthritis, UKR has the advantages of rapid recovery of knee function, less complications and less trauma.The short-term efficacy is satisfactory, but the long-term efficacy remains to be observed.

Clinical Presentation and Outcomes Associated With Fabellectomy in the Setting of Fabella Syndrome.

Background:Clinical outcomes pertaining to isolated lateral fabellectomy in the setting of fabella syndrome are limited to small case reports at this time.Purpose:To assess the most common presenting symptoms, clinical outcomes, and satisfaction after fabella excision in the setting of fabella syndrome.Study Design:Case series; Level of evidence, 4.Methods:Consecutive patients with a minimum of 21-month follow-up after isolated fabellectomy for fabella syndrome were reviewed retrospectively. Clinical outcome scores of the following domains were collected: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Lysholm knee survey, along with a simple numeric patient satisfaction score (range, 1-10; 10 = “very satisfied”). Statistical analysis was performed using paired t tests for all clinical outcome data.Results:A total of 11 isolated fabella excisions were included in 10 patients with isolated lateral-sided knee pain in the setting of fabella syndrome (8 males, 2 females), with a mean age of 36.9 years (range, 23-58 years) and a mean follow-up of 2.4 years (range, 21-47 months). A total of 8 patients (80%) were able to return to full desired activities, including sports. Only 5 of 11 (45%) excisions had concomitant lateral femoral condyle cartilage pathology. There were significant improvements across multiple WOMAC domains, and the WOMAC total score improved from 28.5 ± 17.6 preoperatively to 11.6 ± 10.2 postoperatively (P < .05). Lysholm scores significantly improved from 66.6 ± 23.1 preoperatively to 80.2 ± 13.9 postoperatively (P = .044). Overall patient-reported satisfaction was 8.8 ± 1.6.Conclusion:Fabella excision in the setting of fabella syndrome demonstrated improvements in clinical outcome scores, high rate of returning to preinjury level of activities, and low risk of complications or need for additional surgical procedures.

Age-related changes in the cartilage of the temporomandibular joint.

Osteoarthritis (OA) of the knee is closely associated with aging; however, little is known about the age-related degeneration in the mandibular condylar cartilage (MCC) of the TMJ. Our objective was to examine whether a correlation exists between aging and degeneration of the MCC of the TMJ. Thirty-two male C57BL/6J wild-type mice were aged to 2, 12, 18, and 25months old. The mice were euthanized by CO2 inhalation and were dissected and examined by micro-CT and histology. Sagittal sections of the condyles were stained for tartrate-resistant alkaline phosphatase, alkaline phosphatase, safranin O, picrosirius red, and toluidine blue. In addition, immunostaining for BMP2, BMP4, BMP7, PRG4, and MMP13 was performed. Bone volume fraction and tissue density significantly increased with the age of the animals. There was a significant increase in the Osteoarthritis Research Society International histopathological score and mineralization of the noncalcified cartilage in the aged animals. There was a decrease in cartilage thickness, proteoglycan distribution, and cellularity in the aged animals. Additionally, we noted increased picrosirius red staining with the increase in the age of the animals. Our protein expression showed increased BMP2, BMP4, BMP7, and MMP13, whereas there was a decrease in PRG4 expression in the aged animals. As the animal ages, there is decreased proteoglycan secretion, decreased cellularity, decreased cartilage thickness, increased fibrillation, and increased proteolytic activity. A better understanding of the basic mechanisms underlying the degeneration of the MCC in the older animals could provide novel ways to slow the development of OA.

Effects of occlusion modification on the remodelling of degenerative mandibular condylar processes.

The temporomandibular joint (TMJ) displays a high remodelling capability in response to occlusion changes. The purpose of the current study was to investigate the responses of TMJ condyles of growing mice to the installation of a unilateral anterior crossbite (UAC) prosthesis and the replacement of the UAC prothesis with a bilateral anterior elevation (BAE) prosthesis. C57BL/6J mice were randomly assigned to the blank control and experimental groups. In mice in the experimental groups, UAC was created, while in others, BAE was created after the creation of UAC or removal of UAC. Changes in TMJ condylar cartilage and subchondral bone were assessed. The degradation of condylar cartilage induced by UAC was reversed by BAE, as evaluated by cartilage histochemical changes, collagen II-positive area, collagen X-positive chondrocytes and expression levels of Adamts-5, Mmp13, Tnf-α and Il-1β. Subchondral bone was assessed based on the subchondral bone volume, the number of TRAP-positive cells and the Opg/Rankl ratio. The growing mouse TMJ condyle displays a high remodelling capability, which can be degenerative or rehabilitative in response to the creation of UAC and the replacement of UAC with BAE. Early correction of occlusion is beneficial for the recovery of degenerative condyles.

Knee Arthroscopy: The “Crevice Sign,” a New Pathognomonic Sign for Unstable Posterior Medial Meniscal Tear in Anterior Cruciate Ligament–Deficient Knees

There has been increased emphasis on medial meniscus repair in the anterior cruciate ligament–reconstructed knee, as this improves stability. We describe an arthroscopic sign of an unstable medial meniscal tear that is diagnostic. The “crevice sign” is a longitudinal fissure located on the distal medial femoral condyle. In the anterior cruciate ligament–deficient knee, there is increased strain on the medial meniscus. A posterior longitudinal medial meniscal tear can occur at the time of the index injury or with subsequent instability events. During this injury, the knee pivots and the anterior edge of the unstable medial meniscus digs into the articular cartilage of the medial femoral condyle, resulting in a longitudinal split of the distal femoral condyle articular cartilage. If this sign is observed during arthroscopy, it is recommended that surgeons thoroughly probe the medial meniscus to ensure no pathology is missed.

Tissue interactions are indispensable for cavity formation and disc separation in the temporomandibular joint

ABSTRACT Purpose: Our previous study found that in the temporomandibular joint (TMJ) of the K14-cre; Ctnnb1ex3f mouse embryo, the morphogenesis of glenoid fossa was interrupted by the dislocated condyle. This observation suggested that the formation of the glenoid fossa required tissue interactions with condylar mesenchyme. The purpose of this study was to clarify if the interactions between other components are essential for TMJ morphogenesis. Materials and methods: We examined the gross morphology, histology, cell proliferation, and gene expression in the developing TMJ of K14-cre; Ctnnb1ex3f mice by whole-mount bone and cartilage staining, Azon staining, BrdU labeling, and in situ hybridization, respectively. Results: In K14-cre; Ctnnb1ex3f mice, the zygomatic arch was misconnected to the mandibular bone by ectopic bone formation, which disrupted the attachment of temporalis to the mandibular bone and joint capsule formation. Although the initiation and differentiation of the condylar cartilage were slightly impacted, the K14-cre; Ctnnb1ex3f TMJ lacked joint cavities and separated disc, suggesting that the tissue interactions between the joint capsule and the TMJ were indispensable for the cavity formation and disc separation. The ectopic activation of Gli2 in the cells occupying the cavities, and the enhanced PTHrP transcription in the condylar perichondrium of the K14-cre; Ctnnb1ex3f TMJ suggested that the disrupted interactions between the joint capsule and the TMJ impaired cavity formation and disc separation by altering Hh signaling. Conclusion: Joint capsule formation was essential for cavity formation and disc separation during TMJ development.