YAP promotes the early development of temporomandibular joint bony ankylosis by regulating mesenchymal stem cell function.

To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.

CTGF regulates mineralization in human mature chondrocyte by controlling Pit-1 and modulating ANK via the BMP/Smad signalling.

OBJECTIVE: Connective tissue growth factor (CTGF) exhibits potent proliferative, differentiated, and mineralizing effects, and is believed to be contribute to cartilage mineralization in Osteoarthritis (OA). However, the underlying mechanism of chondrocyte mineralization induced by CTGF remains obscure. As a key regulator of mineral responses, type III phosphate transporter 1 (Pit-1) has been associated with the pathogenesis of articular mineralization. Therefore, the primary objective of this study was to investigate whether CTGF influences the development of mature chondrocyte mineralization and the underlying mechanisms governing such mineralization. METHODS: The effect of Connective tissue growth factor (CTGF) on human C-28/I2 chondrocytes were investigated. The chondrocytes were treated with CTGF or related inhibitors, and transfected with Overexpression and siRNA transfection of Type III Phosphate Transporter 1(Pit-1). Subsequently, the cells were subjected to Alizarin red S staining, PiPer Phosphate Assay Kit, Alkaline Phosphatase Diethanolamine Activity Kit, ELISA, RT-PCR or Western blot analysis. RESULTS: Stimulation with Connective tissue growth factor (CTGF) significantly upregulated the expression of the Type III Phosphate Transporter 1(Pit-1) and mineralization levels in chondrocytes through activation of α5ß1 integrin and BMP/Samd1/5/8 signaling pathways. Furthermore, treatment with overexpressed Pit-1 markedly increased the expression of Multipass Transmembrane Ankylosis (ANK) transporter in the cells. The inhibitory effect of CTGF receptor blockade using α5ß1 Integrin blocking antibody was demonstrated by significantly suppressed the expression of Pit-1 and ANK transporter, as well as chondrocyte mineralization. CONCLUSIONS: Our data indicate that Connective tissue growth factor (CTGF) plays a critical role inchondrocyte mineralization, which is dependent on the expression of the Type III Phosphate Transporter 1(Pit-1) and Multipass Transmembrane Ankylosis (ANK) transporter. Consequently, inhibition of CTGF activity may represent a novel therapeutic approach for the management of Osteoarthritis (OA).

Bone marrow edema in the sacroiliac joints is associated with the development of structural lesions at the same anatomical location over time in patients with axial spondyloarthritis.

OBJECTIVE: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to investigate the association between BME patterns over time and structural lesions in patients with early axial spondyloarthritis (axSpA). METHODS: Patients with axSpA from the DESIR cohort with ≥2 consecutive magnetic resonance imaging (MRI)-SIJ were assessed at baseline, 2 and 5 years. MRI-SIJ images were divided into 8 quadrants. The association between BME and subsequent structural lesions (sclerosis, erosions, fatty lesions, and ankylosis) on MRI in the same quadrant was tested longitudinally. Additionally, patients were grouped according to the pattern of BME evolution across quadrants over time (no BME, sporadic, fluctuating, and persistent). The association between these patterns and 5-year imaging outcomes (eg: ≥5 erosions and/or fatty lesions on MRI-SIJ) was tested. RESULTS: In total, 196 patients were included. BME in each quadrant was associated with sclerosis (OR:1.9 (95%CI: 1.1;3.4)), erosions (1.9 (1.5;2.5)) and fatty lesions (1.9 (1.4;2.6)). Ankylosis was uncommon. There was a gradient between increased level of inflammation and subsequent damage: compared to the 'no BME' pattern, the sporadic (OR (95% CI): 2.1 (1.0;4.5)), fluctuating (OR:5.6(2.2;14.4)) and persistent (OR:7.5(2.8;19.6)) patterns were associated with higher structural damage on MRI-SIJ at 5-years. CONCLUSIONS: In early axSpA, inflammation on MRI-SIJ leads to damage at the quadrant level. The higher the exposure to inflammation across quadrants in the SIJs over time the higher the likelihood of subsequent structural damage, suggesting a cumulative effect.

The predictive effect of neutrophil-lymphocyte and platelet-lymphocyte ratios in the post-operative recurrence of temporomandibular joint ankylosis.

BACKGROUND: Reankylosis is a frequent pathology in patients who are operated for post-traumatic temporomandibular joint (TMJ) ankylosis. In the current practice, ankylosing spondylitis attacks are monitored with the increases in neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). In this study, such a relation between TMJ reankylosis and increase in these ratios was evaluated. METHODS: Patients who were operated between January 2010 and December 2019 for unilateral or bilateral TMJ ankylosis were included in this study. Temporomandibular gap arthroplasty with an interpositional silicone block was performed for each patient by the same operative team. Each patient had standard physiotherapy. All ages and genders were included in the study. Due to the complete blood count differences between children and adults, 18 years of age was used as a cutoff between the groups. A need for reoperation was accepted as reankylosis. The NLR and PLR of children without and with reankylosis and adults without and with reankylosis were compared. RESULTS: Twenty-nine children and 38 adults were included in the study. Mean age of the children and adults were 10.8 and 37.3 years, respectively. Eleven children and eight adults had reankylosis. In patients with reankylosis, NLR and PLR were high significantly, regardless of age. In children, PLR was significantly higher in reankylosis patients. In adults, NLR was significantly higher in reankylosis patients. CONCLUSION: PLR and NLR may be utilized for predicting reankylosis, respectively, in children and adults who were operated for ankylosis due to TMJ fractures.

Platelet-derived growth factor-BB regenerates functional periodontal ligament in the tooth replantation.

Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been proposed as a promising factor for preventing tooth ankylosis. Using rat tooth replantation model, we investigated whether PDGF-BB accelerates the repair of PDL after tooth replantation without ankylosis, and its molecular mechanisms. In PDGF-BB pretreated replanted teeth (PDGF-BB group), ankylosis was markedly reduced and functionally organized PDL collagen fibers were restored; the mechanical strength of the healing PDL was restored to an average of 76% of that in non-replanted normal teeth at 21 days. The numbers of PDGF-Rß- and BrdU-positive cells in the periodontal tissues of the PDGF-BB group were greater than those of atelocollagen pretreated replanted teeth (AC group). Moreover, in the PDGF-BB group, the periodontal tissues had fewer osteocalcin-positive cells and decreased number of nuclear ß-catenin-positive cells compared to those in the AC group. In vitro analyses showed that PDGF-BB increased the proliferation and migration of human periodontal fibroblasts. PDGF-BB downregulated mRNA expressions of RUNX2 and ALP, and inhibited upregulatory effects of Wnt3a on ß-catenin, AXIN2, RUNX2, COL1A1, and ALP mRNA expressions. These findings indicate that in tooth replantation, topical PDGF-BB treatment enhances cell proliferation and migration, and inhibits canonical Wnt signaling activation in bone-tooth ankylosis, leading to occlusal loading of the PDL tissues and subsequent functional restoration of the healing PDL. This suggests a possible clinical application of PDGF-BB to reduce ankylosis after tooth replantation and promote proper regeneration of PDL.

Zygomaticocoronoid ankylosis with possible myositis ossificans: a very rare case.

Ankylosis forming between the zygomatic arch and the coronoid process is a rarely encountered pathological extracapsular ankylosis. Its treatment protocol consists of surgical removal of the coronoid process with the ankylotic mass and jaw opening-closing exercises after surgery. Myositis ossificans (MO) is a self-limiting, benign ossifying lesion. It affects all types of soft tissues including subcutaneous adipose tissue, muscles, tendons and nerves. It is most frequently found in the muscle as a solitary lesion. The clinical appearance of MO is generally in the form of a mass characterized with an ossified soft tissue. When it develops alone, cross-sectional imaging might not be specific, and it may appear similar to worse etiologies. It is suggested multiple imaging modalities should be used in the assessment of a suspicious soft tissue mass. MO is a benign self-limiting disease. In this case report, in the radiographic examination of a 41-year-old female patient, ankylosis between the left coronoid process and the zygomatic bone accompanied by possible MO in the left medial pterygoid muscle was observed. Resection of the coronoid process with the ipsilateral route, resection of the ankylotic mass with the hemicoronal approach and resection of the contralateral coronoid process with the intraoral approach were performed, but the ossified formation in the medial pterygoid muscle was not touched.

Retrospective analysis of a TMJ ankylosis protocol with a 9 year follow up.

OBJECTIVE: Temporomandibular joint ankylosis (TMJa) is a debilitating condition that causes difficulty in mastication, speech and mouth opening. Its treatment poses surgical and rehabilitative challenges along with a high incidence of reankylosis. This study was designed to assess the long-term outcomes with a new two phase physiotherapy protocol following conservative resection of the ankylotic mass. MATERIALS AND METHODS: 143 patients who were treated for TMJa were initially recruited, among whom 98 were inducted into the study and retrospectively evaluated using clinical records and 3-dimensional computed tomography. All the patients underwent a minimal pre auricular incision and conservative interpositional gap arthroplasty with collagen membrane. This was followed by the new two phase physiotherapy protocol with the use of a bite block. The primary outcome measures were the maximum interincisal distance, vertical ramus height and complications. The patients were followed up at monthly intervals during the first year, quarterly intervals during the second year, and at intervals of 6 months during subsequent follow-up years. The mean follow up period was 6.38 ± 2.36 years after ankylotic release. Paired student t test was used for statistical analysis. RESULTS: The mean scores for mouth opening at T1, T2 and T3 were statistically significantly different at all intervals (p < 0.0005). The mean scores for ramal length were statistically significantly different at T1 and T2 interval (p < 0.0005) and insignificant at T2 and T3 interval. No reankylosis was observed in patients who followed the physiotherapy protocol. CONCLUSIONS: In the management of TMJa, the success of the conservative surgical technique with interpositional arthroplasty is less dependent on the longevity and rigidity of the interpositional material but more indebted to the patient compliance in following the proposed physiotherapy protocol.

The role of lateral pterygoid muscle in the traumatic temporomandibular joint ankylosis: A gene chip based analysis.

Traumatic temporomandibular joint ankylosis (TMJA) is a common disease and disorder of the temporomandibular joint (TMJ); however, its pathogenesis has yet to be completely elucidated. In the authors' previous studies, the lateral pterygoid muscle (LPM) was confirmed to exert a function in distraction osteogenesis (DO) during the healing of a condylar fracture, which resulted in the formation of excess bone. The aim of the present study was to investigate alterations in the expression of any associated genes via an Affymetrix GeneChip method. The traumatic TMJA model was fabricated by a condylar fracture in the TMJ area of sheep with either a dissected LPM (LPD) or normal (LPN). The untreated sheep served as a control. At 4­ and 12 weeks post­surgery, the condylar zone was isolated to perform the gene chip analysis, which was performed according to a standard Affymetrix protocol. The validated genes were further evaluated by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The gene chip analysis indicated that the LPN gene expression pattern was similar compared with the DO process, while LPD was similar to that of normal bone fracture healing. The validated genes were collagen type II α1 chain, C­type lectin domain family 3 member A, interleukin 1A, cartilage oligomeric matrix protein, chondromodulin (LECT1), calcitonin receptor (CALCR), transforming growth factor (TGF)­ß1, Fos proto­oncogene (FOS), bone γ­carboxyglutamate protein and bone morphogenic protein (BMP)7, among which, BMP7, LECT1, CALCR and FOS were confirmed by RT­qPCR. In conclusion, the present study demonstrated that LPM exerts a DO effect during the pathogenesis of traumatic TMJA, which may provide a novel target for preventing TMJA.

Ultrasonic versus conventional gap arthroplasty for the release of ankylosis of temporomandibular joint: a prospective cohort study.

The purpose of this study was to compare the clinical outcomes of ultrasonic surgery to the conventional bone cutting technique using bur and saw for the release of ankylosis of temporomandibular joint. We conducted a prospective cohort study on 25 patients with 38 ankylotic joints at Chinese PLA General Hospital from March 01, 2012 to March 01, 2016. Patients were followed up at least 2 years postoperatively. The primary outcome was the intraoperative blood loss per joint. The secondary outcome was the long-term (≥2 years) improvement of maximum mouth opening. The blood loss was significantly reduced in the ultrasonic group compared to the conventional group (107.3 ± 62.3 ml vs. 186.3 ± 92.6 ml, P = 0.019). The long-term improvements of maximum mouth opening were substantial and stable in both groups (33.5 ± 4.8 mm in the ultrasonic group vs. 29.2 ± 6 mm in the conventional group, P = 0.06). Multivariate linear regression analysis showed a significant association between blood loss and technique used (coefficient: 66.3, 95% confidence interval: 22.1,110.4, P = 0.006). The ultrasonic surgery was associated with less intraoperative blood loss when compared to the conventional method for the release of ankylosis of temporomandibular joint while providing a stable and comparable long-term improvement of maximum mouth opening.

Preserving the Fibrous Layer of the Mandibular Condyle Reduces the Risk of Ankylosis in a Sheep Model of Intracapsular Condylar Fracture.

PURPOSE: The aim of this experimental study was to investigate the role of the fibrous layer of the condylar head in the formation of temporomandibular joint (TMJ) ankylosis in a sheep model of intracapsular condylar fracture. MATERIALS AND METHODS: Six growing Xiao-wei Han sheep were used in the study, and bilateral TMJ surgery was performed in each sheep. In the left TMJ, sagittal fracture of the condyle, removal of the fibrous layer of the condylar head, excision of two thirds of the disc, and removal of the fibrous zone of the glenoid fossa were performed. In the right TMJ, the same surgical management was performed, except that in each sheep, the fibrous layer of the condylar head was preserved. Three sheep were killed humanely at 1 month postoperatively, and the other 3 sheep were killed humanely at 3 months postoperatively. The TMJ complexes were examined by histologic evaluation. RESULTS: Fibrous ankylosis was observed on the left side in 3 sheep at 1 month postoperatively and in 2 of 3 sheep at 3 months postoperatively. Fibro-osseous ankylosis was achieved on the left side in 1 sheep at 3 months postoperatively. In the right TMJ, the main postoperative histologic findings included condylar fracture healing, topical rupture or exfoliation of the fibrous layer of the condyle, and fissure between the fibrous layer and the proliferative zone of the condyle. However, no evidence of ankylosis was observed. The TMJ ankylosis scores on the right side were significantly lower than those on the left side at different time points (P < .05). CONCLUSIONS: This study showed that the presence of the fibrous layer of the condylar head prevented the development of TMJ ankylosis in a sheep model of intracapsular condylar fracture.

Cytokines in the pathogenesis of hemophilic arthropathy.

Hemophilic arthropathy (HA) is one of the most common and typical manifestation in the course of recurrent bleeding episodes in patients with hemophilia. Clinical and subclinical joint bleeding episodes gradually lead to irreversible changes manifesting themselves as pain, progressing ankylosis, marked limitation of the range of motion, muscle atrophy and osteoporosis commonly concomitant with joint deformity resulting from chronic proliferative synovitis and both cartilage and bone degeneration leading to the final functional impairment of the joint. In spite of numerous studies, the pathophysiology of HA has not been fully elucidated, especially as regards immunopathological mechanisms which are associated with the subclinical and early stage of the disease and to be more precise, with chronic joint inflammation. It needs to be emphasized that the pathophysiological processes occurring in a joint with HA are most probably highly mediated by interactions within the cytokine network and other inflammatory mediators present in the tissues of affected joint. Among numerous compounds participating in the induction of an inflammatory process in the pathogenesis of HA, cytokines seem to play a leading role. The most important group controlling the disease seems to be well known inflammatory cytokines, including IL-1ß, TNFα and IL-6. The second group with antagonistic effect is formed by anti-inflammatory cytokines such as IL-4 and IL-10. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of HA with respect to cellular and intracellular signaling pathways is still under investigation. This review, summarizes and discusses the current knowledge about cytokine network in the pathogenesis of HA, indicating possible molecular and cellular mechanisms that may provide potential new therapeutic directions.

Ankylosis and pseudoankylosis of the temporomandibular joint in 10 dogs (1993-2015).

OBJECTIVE: To describe the clinical features and results of treatment of true ankylosis and pseudoankylosis of the temporomandibular joint in dogs. METHODS: This study was a retrospective case series. Ten client-owned dogs that were presented for inability to open the mouth or a severely decreased range of motion of the temporomandibular joint were included. Information on the surgical procedures performed and the perioperative complications were documented. Three-dimensional printing of the skull was performed in four dogs. RESULTS: Two dogs were diagnosed with temporomandibular joint ankylosis and seven dogs with pseudoankylosis. One dog had evidence of combined temporomandibular joint ankylosis and pseudoankylosis. Of the seven dogs with pseudoankylosis, six had an osseous fusion involving the zygomatic arch and mandible. Surgical treatment was performed in nine dogs and a revision surgery was needed in one dog. Follow-up ranged from five months to eight years (mean: 48.6 months). Eight out of nine dogs that were treated surgically regained the ability to open their mouth, but six dogs never regained a fully normal temporomandibular joint range of motion. CLINICAL SIGNIFICANCE: Temporomandibular joint ankylosis and pseudoankylosis are uncommon in the dog. Surgical treatment for temporomandibular joint ankylosis or pseudoankylosis in dogs is a successful option and carries a prognosis dependent on patient-specific abnormalities. Computed tomography complemented with three-dimensional printing is valuable for understanding the extent of abnormalities and for preoperative planning.

[Transoral coronoidectomy: Technical note]. / Coronoïdectomie intra-orale: note technique.

INTRODUCTION: Among the skeletal causes of limited mouth opening, uni- or bilateral coronoid process hypertrophy, or Langenbeck disease, is the most frequent. It can be associated with an osteochondroma or a coronoid-malar bone conflict and is then called Jacob disease, an unilateral pathology. Treatment rests on coronoidectomy in both cases. This technique is illustrated via two cases, one Langenbeck and one Jacob disease. TECHNICAL NOTE: A transoral approach was performed. After subperiosteal dissection, the coronoid process was cleared. The process was than severed at its base by means of a burr, freed from its temporal muscular fibers and removed. Mouth opening improved peroperatively. The surgical procedure was completed by active long-term physiotherapy beginning immediately after surgery. DISCUSSION: Transoral coronoidectomy is a simple, quick and safe procedure. Extra-oral approaches present a high risk of facial nerve injury. In our first case, mouth opening improved from 24 to 36 mm after bilateral coronoidectomy and to 40 mm after physiotherapy. In our second case, mouth opening improved from 22 to 38 mm after unilateral coronoidectomy and to 43 mm after one year physiotherapy. Long-term post-operative physiotherapy is mandatory to get and maintain good results.

Total hip arthroplasty through a direct anterior approach for fused hips.

INTRODUCTION: Conversion to total hip arthroplasty (THA) from a fused hip is a challenging procedure because of the technical difficulties involved. Here we report the surgical procedure and the early clinical outcome of conversion THA from a fused hip through a direct anterior approach. METHODS: 9 consecutive THAs following hip fusion were performed in 9 patients. Of these, 6 patients had undergone surgical hip fusion and 3 patients had nonsurgical fusion. RESULTS: The mean time interval between fusion and THA was 29.7 years. The mean follow-up period was 5.2 years. All THAs were performed using a direct anterior approach on a standard surgical table. The mean operative time was 68.7 minutes. The mean intraoperative blood loss was 377 g. All acetabular components were placed within Lewinnek's safe zone. The mean Japanese Orthopaedic Hip Score significantly improved from 54.0 to 73.2. One early anterior dislocation occurred and was treated conservatively. No revision surgery was required. CONCLUSIONS: The direct anterior approach allows for an accurate and less invasive implantation of the total hip components.

Histopathological features of hypertrophic bone mass of temporomandibular joint ankylosis (TMJA): An explanation of pathogenesis of TMJA.

Temporomandibular joint ankylosis (TMJA) is a severe organic disease with progressive limitation of the mouth opening. Histopathologically, a residual joint space is reported to consist of fibrous tissue and/or cartilage, indicating two types of interface (osteo-fibrous and osteo-chondral) of residual joint space. It is well known that adverse mechanical stress results in pathological changes of osteoarthritis and enthesopathy in these interfaces. What would happen pathologically in these interfaces of TMJA under repeated mandible movement has not been elucidated. Fourteen tissue samples of residual joint space and temporal and condylar bone were stained with hematoxylin and eosin and evaluated by collagen I and II immunohistochemistry. A pathological study of 14 TMJA patients showed that the residual joint space presented a fibrocartilage entheses structure and an articular cartilage structure. Moreover, these two structures were associated with pathological alterations of both osteoarthritis and enthesopathy, including degenerated and necrotized tissue, chondrocyte cloning, crack and fissure, various bone scleroses, and inflammatory granulation tissue. It is suggested that the pathological alterations of both osteoarthritis and enthesopathy occurred in TMJA, which hints at mechanical stress on TMJA development.

[3D mandibular distraction planification in a case of severe temporomandibular ankylosis]. / Planification 3D d'une distraction mandibulaire dans le cadre d'une ankylose temporo-mandibulaire sévère.

INTRODUCTION: When occurring in childhood, temporomandibular ankylosis joint is responsible for complex maxillofacial deformities, including mandibular growth deficiency. We present a case of temporomandibular joint ankylosis associated with severe mandibular asymmetry treated by mandibular bone distraction performed under computer assistance. OBSERVATION: A 27-year-old patient presented with a severe facial asymmetry consisting in hypoplasia of the left hemi-mandible and maxilla. Mouth opening was non-existent. The CT-scan showed a left temporomandibular ankylosis. A left mandibular distraction was decided. The distraction characteristics (choice and positioning of the distractor, axis and amount of distraction) were determined preoperatively on the 3D CT-scan. The planning has been transferred to a navigation console (Kolibri®, Brainlab®). A combined intraoral and cutaneous was performed. Navigation allowed for an appropriate placement of the osteotomy line and fixation of the distractor. Distraction was started at the 5th postoperative day at the rate of 1mm per day and lasted 25 days without complication. DISCUSSION: 3D planning allows for better indication setting, better preparation of the procedure, reducing complications and operative time. It may help as an educational tool for young surgeons and for a better understanding from the patient. Navigation is an accurate method for the transfer of the planning in the operation room.

The lateral pterygoid muscle affects reconstruction of the condyle in the sagittal fracture healing process: a histological study.

The purpose of this study was to verify the role of the lateral pterygoid muscle in the reconstruction of the condyle shape during the sagittal fracture healing process by histological methods. Twenty-four adult sheep underwent an osteotomy to create a sagittal fracture of the left condyle; the sheep were then divided randomly into two groups. The lateral pterygoid muscles of the sheep in the experimental group were maintained on the internal poles of the condyles, and their functions remained stable. The lateral pterygoid muscles of the sheep in the control group were cut, and their functions were blocked. The shape, erosion, and calcification of the condyles were observed and measured after 4, 12, and 24 weeks of healing (n=4 from each group). The condyles were then submitted to haematoxylin and eosin, Ponceau S, and Sirius red studies. The results of the histology studies showed increased bone formation in the experimental group in which the functions of the lateral pterygoid muscle remained the same. The results of this study suggest that the lateral pterygoid muscle affects the reconstruction of the condylar shape during the healing process of a sagittal fracture of the mandibular condyle, and may even be involved in the formation of ankylosis.

Interleukin-17 is a critical target for the treatment of ankylosing enthesitis and psoriasis-like dermatitis in mice.

Ankylosis is a major pathological manifestation of spondyloarthropathy. The aim of this study was to evaluate the effects of anti-IL-17 therapy on spontaneous ankylosing enthesitis in mice. In this study, we used male DBA/1 mice as a spontaneous ankylosis model. Serum IL-17 concentrations were determined using enzyme-linked immunosorbent assay. Male DBA/1 mice from different litters were mixed and caged together preceding the treatment at 10 weeks (wk) of age (prophylaxis) or 21 wk of age (intervention). Treatment with anti-IL-17 antibodies or saline was initiated after caging in groups of mice and administered weekly. The onset of tarsal ankylosis was assessed by ankle swelling and histopathological examination. Pathological changes and mRNA expression levels were assessed in joints and ears obtained at the experimental end-point. We found that circulating IL-17 increased with the onset of ankylosis in male DBA/1 mice, coinciding with the onset of dermatitis. The symptoms of dermatitis corresponded to the pathological characteristics of psoriasis: acanthosis with mild hyperkeratosis, scaling, epidermal microabscess formation and augmented expression of K16, S100A8 and S100A9. Prophylactic administration of anti-IL-17 antibodies significantly prevented the development of both ankylosis and dermatitis in male DBA/1 mice caged together. On the other hand, administration of anti-IL-17 antibodies after disease onset had a lesser but significant effect on ankylosis progression but did not affect dermatitis progression. In conclusion, IL-17 is a key mediator in the pathogenic process of tarsal ankylosis and psoriasis-like dermatitis in male DBA/1 mice caged together. Thus, IL-17 is a potential therapeutic target in ankylosing enthesitis and psoriasis in humans.

Approach to the diagnosis of unusual carpal ankylosis from ancient Egypt.

OBJECTIVES: Carpal fusion is not an uncommon finding in archaeological bones. The majority of cases are due to inflammatory or infectious diseases and those are usually associated with other major alterations in the skeleton. METHODS: Two distinct individual cases, both adult females recovered from the Necropolis of Sharuna in the Middle Egypt from the Ptolemaic Period (IV to I BC) are presented in this study. Specimen 4323/1 shows a fusion of the scaphoid, lunate and triquetral bones in the right wrist. Specimen 4323/2 is a very rare fusion of a dysplastic lunate bone with the radius in the left wrist. In the proximal end of that left wrist, two possible remains of the flattened scaphoid and triquetral bones are also present. RESULTS: A differential diagnosis of both abnormalities as well as broad research into similar paleopathological cases were carried out: the most probable diagnosis for the specimen 4323/1 is an uncommon carpal coalition of three bones from the same row; the diagnosis of the specimen 4323/2 is more dubious with both rheumatoid arthritis and septic arthritis being strong candidates. CONCLUSIONS: In archaeological remains, carpal fusion should be thoroughly studied in order to ensure an accurate differential diagnosis.

Bone lineage proteins in the entheses of the midfoot in patients with spondyloarthritis.

OBJECTIVE: Patients with juvenile-onset spondyloarthritis (SpA) may develop ankylosis of the midfoot resembling the spinal changes seen in patients with ankylosing spondylitis (AS). The study of the histopathology of the feet of patients with tarsitis could help us understand the pathogenesis of bone formation in affected structures in the SpA. The objective of our study was to describe the histopathologic characteristics of the midfoot in patients with tarsitis associated with SpA. METHODS: We obtained synovial sheaths, entheses, and bone samples from 20 patients with SpA with midfoot pain/tenderness and swelling. Tissue samples underwent H&E staining; immunohistochemistry for CD3, CD4, CD8, CD68, and CD20 cell identification; and immunofluorescence for bone lineage proteins, including osteocalcin, osteopontin, parathyroid hormone-related protein, bone sialoprotein, and alkaline phosphatase. RESULTS: Slight edema and hyalinization were found in some tendon sheaths, and few inflammatory cells were detected in the entheses. In bones, we found some changes suggesting osteoproliferation, including endochondral and intramembranous ossification, but no inflammatory cells. In entheses showing bone proliferation, we detected osteocalcin and osteopontin in cells with a fibroblast-mesenchymal phenotype, suggesting the induction of entheseal cells toward an osteoblast phenotype. CONCLUSION: Osteoproliferation and abnormal expression of bone lineage proteins, but no inflammatory infiltration, characterize midfoot involvement in patients with SpA. In this sense, tarsitis (or ankylosing tarsitis) resembles the involvement of the spine in patients with AS. Ossification may be in part explained by the differentiation of mesenchymal entheseal cells toward the osteoblastic lineage.