Effect of Mechanical Stress on Rheumatoid Arthritis of the Temporomandibular Joint: a Morphological and Histological Evaluation

2021 ◽  
Author(s):  
Kohei Nagai ◽  
Takenobu Ishii ◽  
Yasushi Nishii
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Mechanical Stress ◽  
Temporomandibular Joint ◽  
Mandibular Condyle ◽  
Γδ T Cells ◽  
Histological Evaluation ◽  
Control Group ◽  
Condylar Cartilage ◽  
Layer Width

Abstract Background Rheumatoid arthritis of the temporomandibular joint (TMJ-RA) has been reported to have a larger incidence range than systemic rheumatoid arthritis (RA). The presence or absence of mechanical stress (MS) is considered a factor in this. In this study, we hypothesized that TMJ-RA develops or worsens when excessive MS is applied to the temporomandibular joint of RA mouse models. We aimed to clarify the relationship between TMJ-RA and MS through morphological and histological evaluation. Methods Collagen antibody-induced arthritis (CAIA) was induced in male DBA/1JNCrlj 9–12 weeks old mice by administering Type II collagen antibody and lipopolysaccharide to produce RA model mice. MS was applied to the mandibular condyle. The group was separated into non-RA (control group (N = 5) and MS group (N = 5)), and RA group (CAIA group (N = 5)and CAIA MS group (N = 5)). To confirm the morphological changes in the mandibular condyle, micro-CT imaging was performed. Histological evaluation of the TMJ was performed by hematoxylin and eosin staining for condylar cartilage cell layer thickness, Safranin O staining for proteoglycans, and tartrate-resistant acidic phosphatase staining for osteoclast count. Immunohistochemical evaluation was performed to assess the localization of cartilage destruction enzymes using ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) antibody. Additionally, CD3 (cluster of differentiation), CD45, and γδ TCR (T cell receptor) antibodies were used to localize and identify the type of lymphocytes. Results In the CAIA MS model, a three-dimensional analysis of the temporomandibular joint by microcomputer tomography showed a crude change in the surface of the mandibular condyle. Histological examination revealed a decrease in the chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. T cell accumulation was observed, and γδ T cell involvement was confirmed. Conclusions In the CAIA model, the TMJ was less sensitive to the initiation of RA. However, the results suggested that it was exacerbated by MS, and that γδ T cells may be involved in TMJ-RA.

scholarly journals Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheumatoid Arthritis: A Morphological and Histological Evaluation

2022 ◽  
Vol 12 ◽  
Author(s):  
Kohei Nagai ◽  
Takenobu Ishii ◽  
Tatsukuni Ohno ◽  
Yasushi Nishii
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Mouse Model ◽  
Mandibular Condyle ◽  
Γδ T Cells ◽  
Histological Evaluation ◽  
Micro Ct ◽  
Layer Width ◽  
Temporomandibular Joints ◽  
Histological Staining

Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9−12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.

Parathyroid hormone promotes cartilage healing after free reduction of mandibular condylar fractures by upregulating Sox9

2021 ◽  
pp. 153537022110271
Author(s):  
Yuanyuan Jia ◽  
Liuqin Xie ◽  
Zhenglong Tang ◽  
Dongxiang Wang ◽  
Yun Hu ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Internal Fixation ◽  
Early Stage ◽  
Rabbit Model ◽  
Mandibular Condyle ◽  
Fracture Site ◽  
Control Group ◽  
Condylar Cartilage ◽  
Cartilage Healing ◽  
Experimental Group

After high fractures of the mandibular condyle, the insufficient blood supply to the condyle often leads to poor bone and cartilage repair ability and poor clinical outcome. Parathyroid hormone (PTH) can promote the bone formation and mineralization of mandibular fracture, but its effects on cartilage healing after the free reduction and internal fixation of high fractures of the mandibular condyle are unknown. In this study, a rabbit model of free reduction and internal fixation of high fractures of the mandibular condyle was established, and the effects and mechanisms of PTH on condylar cartilage healing were explored. Forty-eight specific-pathogen-free (SPF) grade rabbits were randomly divided into two groups. In the experimental group, PTH was injected subcutaneously at 20 µg/kg (PTH (1–34)) every other day, and in the control group, PTH was replaced with 1 ml saline. The healing cartilages were assessed at postoperative days 7, 14, 21, and 28. Observation of gross specimens, hematoxylin eosin staining and Safranin O/fast green staining found that every-other-day subcutaneous injection of PTH at 20 µg/kg promoted healing of condylar cartilage and subchondral osteogenesis in the fracture site. Immunohistochemistry and polymerase chain reaction showed that PTH significantly upregulated the chondrogenic genes Sox9 and Col2a1 in the cartilage fracture site within 7–21 postoperative days in the experimental group than those in the control group, while it downregulated the cartilage inflammation gene matrix metalloproteinase-13 and chondrocyte terminal differentiation gene ColX. In summary, exogenous PTH can stimulate the formation of cartilage matrix by triggering Sox9 expression at the early stage of cartilage healing, and it provides a potential therapeutic protocol for high fractures of the mandibular condyle.

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

2020 ◽  
Vol 42 (6) ◽  
pp. 658-663
Author(s):  
Xiyuan Guo ◽  
Ippei Watari ◽  
Yuhei Ikeda ◽  
Wu Yang ◽  
Takashi Ono
Keyword(s):  
Hyaluronic Acid ◽  
Articular Cartilage ◽  
Temporomandibular Joint ◽  
Experimental Period ◽  
Lateral Shift ◽  
Control Group ◽  
Condylar Cartilage ◽  
Growing Rats ◽  
Shift Group ◽  
Recovery Group

Summary Background 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. Methods 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. Results 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. Limitations This research was based on animal experiments with a limited experimental period. Conclusion FLSM altered lubrication related HA metabolism in the articular cartilage of the TMJ in growing rats.

TMJ imaging: more pictures, less talk

2011 ◽  
Vol 2 (4) ◽  
pp. 172-182 ◽  
Author(s):  
Jimmy Makdissi de C Williams
Keyword(s):  
Rheumatoid Arthritis ◽  
Skull Base ◽  
Temporomandibular Joint ◽  
Temporal Bone ◽  
Mandibular Condyle ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Number Of Factors ◽  
Muscles Of Mastication ◽  
Anatomical Area

The temporomandibular joint (TMJ) is a complex anatomical area consisting of the mandibular condyle and the temporal bone of the skull base. It comes under the influence of a number of factors including the muscles of mastication, teeth, occlusion and the contralateral joint and thus there exists a spectrum of conditions. Internal derangement and degenerative joint disease remain the most common although there are a range of other less frequently occurring conditions such as rheumatoid arthritis, trauma and ankylosis.

scholarly journals Therapeutic effect of various ginsenosides on rheumatoid arthritis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Meng Zhang ◽  
Hongwei Ren ◽  
Kun Li ◽  
Shengsheng Xie ◽  
Ru Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
T Cell ◽  
Therapeutic Effect ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Potential Candidate ◽  
Tnf Α ◽  
Huvec Cells

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug. Methods The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA. In in vitro cell studies, methotrexate (MTX) and 0.05% dimethyl sulfoxide (DMSO) was set as a positive control group and a negative control group, respectively. LPS-induced RAW264.7 cells and TNF-α-induced HUVEC cells were cultured with MTX, DMSO and six ginsenosides, respectively. Cell proliferation was analyzed by MTT assay and cell apoptosis was carried out by flow cytometry. CIA mice model was developed to evaluate the therapeutic efficacy of ginsenosides. The analysis of histology, immunohistochemistry, flow cytometry and cytokine detections of the joint tissues were performed to elucidate the action mechanisms of ginsenosides. Results All six ginsenosides showed good therapeutic effect on acute arthritis compared with the negative control group, Ginsenoside CK provided the most effective treatment ability. It could significantly inhibit the proliferation and promote the apoptosis of RAW 264.7 and HUVEC cells, and substantially reduce the swelling, redness, functional impairment of joints and the pathological changes of CIA mice. Meanwhile, CK could increase CD8 + T cell to down-regulate the immune response, decrease the number of activated CD4 + T cell and proinflammatory M1-macrophages, thus resulting in the inhibition of the secretion of proinflammatory cytokine such as TNF-α and IL-6. Conclusion Ginsenoside CK was proved to be a most potential candidate among the tested ginsenosides for the treatment of RA, with a strong anti-inflammation and immune modulating capabilities.

scholarly journals Assessment of bone marrow fat fractions in the mandibular condyle head using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246596
Author(s):  
Kug Jin Jeon ◽  
Chena Lee ◽  
Yoon Joo Choi ◽  
Sang-Sun Han
Keyword(s):  
Bone Marrow ◽  
Least Squares ◽  
Temporomandibular Joint ◽  
Mandibular Condyle ◽  
Least Squares Estimation ◽  
Control Group ◽  
Dixon Method ◽  
Iterative Decomposition ◽  
Iq Method ◽  
Decomposition Of Water

The prevalence of temporomandibular joint disorder (TMD) is gradually increasing, and magnetic resonance imaging (MRI) is becoming increasingly common as a modality used to diagnose TMD. Edema and osteonecrosis in the bone marrow of the mandibular condyle have been considered to be precursors of osteoarthritis, but these changes are not evaluated accurately and quantitatively on routine MRI. The iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method, as a cutting-edge MRI technique, can separate fat and water using three asymmetric echo times and the three-point Dixon method. The purpose of this study was to analyze the quantitative fat fraction (FF) in the mandibular condyle head using the IDEAL-IQ method. Seventy-nine people who underwent MRI using IDEAL-IQ were investigated and divided into 1) the control group, without TMD symptoms, and 2) the TMD group, with unilateral temporomandibular joint (TMJ) pain. In both groups, the FF of the condyle head in the TMJ was analyzed by two oral and maxillofacial radiologists. In the TMD group, 29 people underwent cone-beam computed tomography (CBCT) and the presence or absence of bony changes in the condylar head was evaluated. The FF measurements of the condyle head using IDEAL-IQ showed excellent inter-observer and intra-observer agreement. The average FF of the TMD group was significantly lower than that of the control group (p < 0.05). In the TMD group, the average FF values of joints with pain and joints with bony changes were significantly lower than those of joints without pain or bony changes, respectively (p < 0.05). The FF using IDEAL-IQ in the TMJ can be helpful for the quantitative diagnosis of TMD.

scholarly journals Hypoxia-inducible Factor Expression Is Related to Apoptosis and Cartilage Degradation in Temporomandibular Joint Osteoarthritis

2022 ◽  
Author(s):  
Jun Zhang ◽  
Yu Hu ◽  
Zihan Wang ◽  
Xuelian Wu ◽  
Chun Yang ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Expression Patterns ◽  
Cartilage Damage ◽  
Hypoxia Inducible Factor ◽  
Cartilage Degeneration ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Condylar Cartilage ◽  
Hypoxic Conditions ◽  
Temporomandibular Joint Osteoarthritis

Abstract Background: It remains unclear whether hypoxic conditions affect apoptosis and contribute to degradation of cartilaginous tissues in osteoarthritis (OA) lesions. In this study, we hypothesized that hypoxic conditions induced the accumulation of hypoxia-inducible factor (HIF) and activated apoptosis to contribute to OA cartilage degeneration in vivo.Methods: Malocclusion stress was applied for 2 weeks, 4 weeks and 8 weeks to induce an OA-like lesion animal model (OD) in rats. Histological analysis was performed by H&E staining and safranin O/fast green staining. The expression levels of protein in condylar cartilage were examined by immunostaining to evaluate cartilage degeneration.Results: We found apparent histological phenotypes associated with degeneration in the occlusion disorder stress (OD) group. The OD group at 4 weeks and 8 weeks had obviously reduced expression of Acan and Col II in cartilage. In contrast, the OD groups had higher levels of Col X, ADAMTS5 and MMP13 in the condylar cartilage than the control group. Moreover, the OD group cartilage had prominent degenerative changes with reduced levels of HIF1α and increased levels of HIF2α and the apoptosis factor Caspase3 in condylar cartilage at 8 weeks.Occlusion disorder stress results in cartilage degeneration. HIF1α and HIF2α are involved in temporomandibular joint (TMJ) cartilage homeostasis by regulating chondrocyte apoptosis, which contributes to TMJ cartilage degeneration. Conclusion: Thus, abnormal hypoxic conditions inducing opposite expression patterns of HIF1α and HIF2α could be involved in the pathogenesis of condylar cartilage degeneration. HIF2α may provide a potential negative feedback mechanism for HIF1α during cartilage damage.

scholarly journals The Effect of Overexpression of Lrp5 on the Temporomandibular Joint

Cartilage ◽  
2020 ◽  
pp. 194760352096887
Author(s):  
Achint Utreja ◽  
Hengameh Motevasel ◽  
Carol Bain ◽  
Robert Holland ◽  
Alexander Robling
Keyword(s):  
Temporomandibular Joint ◽  
Subchondral Bone ◽  
Wnt Pathway ◽  
Mandibular Condyle ◽  
Cartilage Thickness ◽  
Bone Volume ◽  
Missense Mutations ◽  
Micro Computed Tomography ◽  
Condylar Cartilage ◽  
High Bone Mass

Objective The temporomandibular joint (TMJ) is a unique fibrocartilaginous joint that adapts to mechanical loading through cell signaling pathways such as the Wnt pathway. Increased expression of low-density lipoprotein receptor-related protein 5 (Lrp5), a co-receptor of the Wnt pathway, is associated with a high bone mass (HBM) phenotype. The objective of this study was to analyze the effect of overexpression of Lrp5 on the subchondral bone and cartilage of the TMJ in mice exhibiting the HBM phenotype. Design Sixteen-week-old Lrp5 knock-in transgenic mice carrying either the A214V (EXP-A) or G171V (EXP-G) missense mutations, and wildtype controls (CTRL) were included in this study. Fluorescent bone labels, calcein, alizarin complexone, and demeclocycline were injected at 3.5, 7.5, and 11.5 weeks of age, respectively. The left mandibular condyle was used to compare the subchondral bone micro-computed tomography parameters and the right TMJ was used for histological analyses. Cartilage thickness, matrix proteoglycan accumulation, and immunohistochemical localization of Lrp5 and sclerostin were compared between the groups. Results Subchondral bone volume (BV) and percent bone volume (BV/TV) were significantly increased in both EXP-A and EXP-G compared with CTRL ( P < 0.05) whereas trabecular spacing (Tb.Sp) was decreased. Cartilage thickness, extracellular matrix production, and expression of Lrp5 and Sost were all increased in the experimental groups. The separation between the fluorescent bone labels indicated increased endochondral maturation between 3.5 and 7.5 weeks. Conclusions These data demonstrate that Lrp5 overexpression leads to adaptation changes in the mandibular condylar cartilage of the TMJ to prevent cartilage degradation.

scholarly journals Association of γδ T Cells with Disease Severity and Mortality in Septic Patients

2013 ◽  
Vol 20 (5) ◽  
pp. 738-746 ◽  
Author(s):  
Juan C. Andreu-Ballester ◽  
Constantino Tormo-Calandín ◽  
Carlos Garcia-Ballesteros ◽  
J. Pérez-Griera ◽  
Victoria Amigó ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymphocyte Subsets ◽  
Γδ T Cells ◽  
T Cell Subsets ◽  
Control Group ◽  
Gamma Delta T Cells ◽  
Γδ T Cell ◽  
Gamma Delta ◽  
First Line

ABSTRACTGamma-delta T cells are the most abundant of all epithelial-resident lymphocytes and are considered a first line of defense against pathogens in the mucosa. Our objective was to confirm the reduction in γδ T cell subsets and its relationship with mortality in patients with sepsis. We studied 135 patients with sepsis attended in the emergency department and intensive care unit of two hospitals and compared them with a similar control group of healthy subjects. The αβ and γδ T cell subsets were determined via flow cytometry according to the stage of the sepsis and its relationship with mortality. All the lymphocyte subsets were reduced with respect to the corresponding subsets in the control group. All the γδ T cell populations decreased significantly as the septic picture worsened. Furthermore, γδ T cells showed decreases at days 2, 3, and 4 from the start of sepsis. Twenty-six patients with sepsis died (19.3%). The γδ T cells, specifically, the CD3+CD56+γδ T cells, were significantly reduced in those septic patients who died. Our results indicate that, during sepsis, γδ T cells show the largest decrease and this reduction becomes more intense when the septic process becomes more severe. Mortality was associated with a significant decrease in γδ T cells.

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