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Background: Temporomandibular joint osteoarthritis (TMJOA) is characterized by articular cartilage degeneration and progressive synovitis. How to effectively inhibit TMJOA in the early stage has been a hot topic in the biomedical field. As a non‐invasive physiotherapy, pulsed electromagnetic field (PEMF) treatment has shown great potential in the treatment of osteoarthritis (OA) in extremity joints. Objective: This study aims to investigate the biological effect of PEMF intervention on TMJ cartilage degeneration and synovium inflammation at the early stage of TMJOA. Methods: PEMF (2.0 mT, 15 Hz, 2 h/day) treatment was given to rats in which TMJOA was induced by applying the unilateral anterior crossbite (UAC). Histological and immunohistochemical staining, TUNEL assay, real‐time PCR and western blotting assay were performed to detect the changes of the morphology and the expression of pro‐inflammatory and degradative factors in condylar cartilage and synovium. Results: Obvious condylar cartilage degeneration, characterized by decreased cartilage thickness, degraded cartilage extracellular matrix, increased expression of pro‐inflammatory and degradative factors (TNF‐α, IL‐1β, MMP‐13, ADAMTS‐5, IL‐6, MMP‐3, MMP‐9 and COL‐X) and increased chondrocytes death, was observed in UAC group, accompanied by synovium hyperplasia and up‐regulation of pro‐inflammatory and degradative factors in synovium. PEMF intervention reversed the decreased cartilage thickness at 3 weeks and degraded cartilage extracellular matrix at 6 weeks. Moreover, the up‐regulation of pro‐inflammatory, degradative and hypertrophyic factors and chondrocytes death in condylar cartilage induced by UAC were inhibited to some extent. In addition, the synovium hyperplasia and the up‐regulation of pro‐inflammatory and degradative factors in synovium were inhibited at 3 weeks and 6 weeks. Conclusions: Appropriate PEMF stimulation can reverse the loss of cartilage extracellular matrix, the chondrocytes death, the increased expression of pro‐inflammatory and degradative factors in cartilage, the decreased cartilage thickness and synovium inflammation induced by UAC at the early stage of TMJOA to some extent. PEMF stimulation may be a promising method in clinical TMJOA treatment. [ABSTRACT FROM AUTHOR]

Objective: Incisors tubed prosthesis with bilateral anterior elevation (BAE) relation had been reported to stimulate the proliferative response in the mandibular condylar cartilage of mice, thus the prosthetic occlusion elevation had been proposed to treat cartilage degeneration. Currently, we aimed to detect the long‐term effect of BAE on temporomandibular joints (TMJs). Materials and Methods: Twelve 6‐week‐old female mice were assigned to age‐matched control and BAE groups (n = 6). Micro‐CT images and the macro‐ and micro‐morphology of the mandibular condyles were analyzed at 29 weeks. Results: Compared with the age‐matched controls, in BAE group, there were loss of subchondral cortical bone and heavy loss of the subchondral trabecular bone at the superior sites of the TMJ condyles, but hyperostosis at the inferior sites as revealed by micro‐CT images and histological slices. In BAE group, cartilage thickness and matrix area were increased with upregulated expression of type II, type X collagen, and Ki67, but the expression of cleaved caspase‐3 was downregulated (all, p < 0.05). Conclusion: In addition to cartilage thickening, long‐term BAE induces loss of the subchondral cortical bone and heavy loss of the underneath subchondral trabecular bone, but hyperostosis further underneath. Using BAE as a treatment remains double‐edged. [ABSTRACT FROM AUTHOR]

Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective: We aimed to develop a mouse model predominating in a proliferative response in the articular cartilage of the temporomandibular joints. Materials and Methods: Bilateral anterior elevation of occlusion was developed by installing metal tubes onto the incisors of mice with edge‐to‐edge relation to prevent tooth wear, leading to an increase in the vertical height of the dental occlusion with time. Morphological changes and expression changes in Cyclin D1, Aggrecan, and type II and type X collagen in the mandibular condylar cartilage were detected. In addition, cells were isolated from the mandibular condylar cartilage and exposed to cyclic tensile strain (CTS). Results: Compared with age‐matched controls, the tooth length was longer at 3 weeks, 7 weeks, and 11 weeks in BAE mice (p < 0.05), with increased condylar cartilage thickness, matrix amount, and cell number (p < 0.05). Compared with the deep zone cells, CTS stimulated the superficial zone cells to express a higher level of proliferating cell nuclear antigen, Cyclin D1, Aggrecan, and type II collagen but a lower level of type X collagen and alkaline phosphatase. Conclusion: Bilateral anterior elevation stimulated the proliferative response in the mandibular condylar cartilage, offering a new therapeutic strategy for cartilage degeneration. [ABSTRACT FROM AUTHOR]

Highlights • Insulin like growth factor-1 is increased in the degenerative cartilage. • Insulin like growth factor-1 receptor is increased in degenerative cartilage. • Insulin like growth factor binding protein-3 is dual in degenerative cartilage. • Insulin like growth factor binding protein-5 is increased in degenerative cartilage. • Occlusion stimulates insulin like growth factor-1 expression in jaw joint cartilage. Abstract Objective To investigate the changes in insulin-like growth factor-1 (IGF-1) expression levels in the degenerative mandibular condylar cartilage. Design Thirty-six rats were divided into the unilateral anterior crossbite and control groups. The expression levels of IGF-1; IGF-1 receptor (IGF-1R); IGF-binding protein-3 and -5 (IGFBP-3 and -5); proliferating cell nuclear antigen (PCNA); aggrecan; type-I, -II, -VI, and -X collagen; tissue inhibitor of metalloproteinases-1 and -3 (TIMP-1 and -3); metalloproteinases of matrix metalloproteinases-3 and-13 (MMP-3 and -13); a disintegrin and metalloproteinase thrombospondin-4 and -5 (ADAMTS-4 and -5); alkaline phosphatase (ALP); β-glucuronidase; and N-acetyl-β-glucosaminidase in the mandibular condylar cartilage were assessed. Results The protein expression levels of IGF-1and IGF-1R were increased from week 4 in the unilateral anterior crossbite group. The mRNA expression level of IGFBP-3 and -5 was upregulated from week 4 and week 2, respectively; that of IGFBP-3 was downregulated at week 8; and that of PCNA, type-II collagen, type-X collagen, aggrecan, TIMP-1, and TIMP-3 was downregulated, whereas that of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, β-glucuronidase, and N-acetyl-β-glucosaminidase were upregulated from week 2. The positive area size of type-I collagen was increased and that of type VI collagen was decreased from week 2. The positive area size of type X collagen was increased at week 2 but decreased at week 8. The percentage of ALP-positive cells was increased from week 4. Conclusions Unilateral anterior crossbite stimulated the multifarious expression of IGF-1 and IGFBP, which may be linked to chondrocyte proliferation and differentiation in the mandibular condylar cartilage that showed progressive degeneration. [ABSTRACT FROM AUTHOR]

Cells in articular cartilage are zonal arranged. Cells in superficial zone cartilage are generally small and proliferative. Appropriate negative pressure stimulation is beneficial to cell survival and tissue repair. Whether negative pressure has promotive impact on the proliferation activity of the superficial zone chondrocytes is of interest. In this study, we isolated superficial chondrocytes from the mandibular condylar cartilage of rats. After negative pressure treatment, the cells were collected for RNA-sequencing, quantitative real-time PCR and western blotting assays, aiming to detect the proliferative responses of chondrocytes to negative pressure and explore the potential molecular mechanisms. Data from RNA-sequencing analysis indicated that the superficial chondrocytes responded to the 4 h −10 kPa treatment by a significant increase in proliferation. In addition, the expression of high-mobility group box 2 (HMGB2) and the phosphorylation of AKT were obviously promoted. Knockdown of HMGB2 decreased AKT phosphorylation and diminished the negative pressure-induced proliferation of chondrocytes, as shown by decreased expression of Ki67 and cyclin-dependent kinase 6 (CDK6). In contrast, overexpression of HMGB2 enhanced AKT phosphorylation and further promoted proliferative activity. Moreover, LY294002, an AKT inhibitor, suppressed the proliferative activity of chondrocytes under negative pressure, while SC79, an activator of AKT phosphorylation, enhanced the proliferation of chondrocytes. Our data demonstrated that HMGB2 exhibits a promotion impact on chondrocyte proliferation under negative pressure via the phosphorylation of AKT. These results provide a new perspective for superficial zone chondrocytes proliferation under negative pressure, which should be benefit for cartilage regeneration. • Negative pressure is beneficial for superficial chondrocytes of TMJ condyle to proliferate. • HMGB2 activated chondrocyte proliferation under negative pressure through the activation of AKT. • The effective activation of chondrocyte proliferation could be a promising way to treat cartilage degeneration diseases. [ABSTRACT FROM AUTHOR]

• Obvious OA-like lesion can be induced by unilateral anterior crossbite (UAC). • High level of oestrogen could aggravate the degenerative changes of condylar cartilage in TMJ OA. • The effect of oestrogen on condylar cartilage is at least partially via oestrogen-ERβ-HIF2α pathway. Oestrogen and hypoxia inducible factor-2α (HIF2α) are key regulators in the pathogenesis of osteoarthritis (OA). However, the cellular interaction between oestrogen and HIF2α in articular cartilage during OA process remains unknown. Our previous study has revealed that high-physiological level of oestrogen aggravates the degradation of condylar cartilage in the early stage of temporomandibular joint osteoarthritis (TMJ OA). Here, we hypothesize that HIF2α involves the effect of oestrogen on mandibular condylar cartilage in the progression of TMJ OA. Our experiment in vivo found that the degeneration of condylar cartilage caused by unilateral anterior crossbite (UAC) model, characterized by obvious degenerative morphology, loss of cartilage extracellular matrix, up-regulation of TNF-α, HIF2α and its' down-stream OA-related cytokines (MMP-13, VEGF and Col X), could be alleviated by lack of oestrogen while aggravated by high level of oestrogen in rats. Meanwhile, our in vitro study found that 17β-estradiol stimulation resulted in the loss of extracellular matrix, increased expression of TNF-α, IL-1, HIF2α and its' down-stream OA-related cytokines (MMP-13, VEGF and Col X) in primary condylar chondrocytes via oestrogen receptor beta (ERβ), which could be reversed by ER antagonist, selective estrogen receptor modulators (SERMs) and HIF2α translation inhibitor. Our results reveal that high level of oestrogen can aggravate the degenerative changes of mandibular condylar cartilage, while lack of oestrogen can alleviate it via oestrogen-ERβ-HIF2α pathway during TMJ OA progression. [ABSTRACT FROM AUTHOR]