Activation of kappa opioid receptor suppresses post-traumatic osteoarthritis via sequestering STAT3 on the plasma membrane.

OBJECTIVE: Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. METHODS: U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). RESULTS: OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1ß and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. CONCLUSIONS: KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA.

Results of radiological follow-up of untreated anterior disc displacement without reduction in adolescents.

Our aim was to assess the progression of disease without treatment in adolescents with non-reducible anterior disc displacement (ADD) using serial magnetic resonance images (MRI). We retrospectively reviewed all patients under the age of 20 years who had unilateral non-reducible ADD and had had two MRI during a period of 6 months with no intervention. A total of 124 patients (101 female and 23 male) with a mean (range) age of 16 (10-20) years had 2 MRI at least 6 months apart (mean (range) 14 (6-47) months). At the initial visit there was a significant difference between the involved and the non-involved sides in the incidence of condylar degeneration and effusion (p=0.0001). The effusion significantly decreased despite the lack of intervention, the amount of disc deformation significantly increased (p=0.003), and the degree of condylar degeneration increased from 61%-69%, but this did not differ significantly. We conclude that during the period of observation there was a significant reduction in the incidence of effusion and significant increase in disc deformation. Whilst there was an increase in the changes on the condylar surface, this was not significant.

Is anterior disc displacement without reduction associated with temporomandibular joint condylar height in juvenile patients younger than 20 years?

PURPOSE: Because disc displacement might be accompanied by degenerative changes in the condyle, this study explored the association between condylar height and anterior disc displacement without reduction in juvenile patients. MATERIALS AND METHODS: This was a retrospective cohort study that enrolled a sample of patients younger than 20 years with unilateral disc displacement without reduction. All patients had 2 magnetic resonance imaging records taken from January 2010 to June 2013 (interval, >6 months). Condylar height, disc length, and displacement distance were measured. The predictor variable was joint status (healthy vs affected side), and the outcome variables were changes in condylar height, displacement distance, and disc length over time. SAS 9.13 was used for analysis and the P value was set at .05. RESULTS: One hundred twenty-four patients (101 female and 23 male; mean age, 16.4 yr; mean interval, 13.6 months) were included. During the interval, the condylar height of the healthy side increased 0.75 mm, whereas the condylar height of the affected side decreased 0.41 mm. The disc of the affected side was shortened and more anteriorly displaced. CONCLUSION: Anterior disc displacement without reduction could be accompanied by a decrease in condylar height in juvenile patients, and the disc might be shortened and more anteriorly displaced.

Pigmented villonodular synovitis of the temporomandibular joint with intracranial extension.

Pigmented villonodular synovitis is an uncommon benign tumor-like proliferative lesion with an undetermined origin. Involvement of the temporomandibular joint is uncommon. Although pigmented villonodular synovitis is a benign lesion, it can grow with an aggressive pattern, and it extends extra-articularly in most of the reported cases, about one-third of them exhibiting intracranial involvement. The authors reported an additional case of a 47-year-old woman with intracranial extension, who had a history of joint pain and trismus. The preoperative diagnosis was made with arthroscopy. The lesion was completely excised via preauricular approach and condylotomy. The bone defect was covered by the pedicled temporalis myofascial fat flap. The patient has been symptom-free for 40 months postoperatively.