Jumonji domain containing-3 (JMJD3) inhibition attenuates IL-1ß-induced chondrocytes damage in vitro and protects osteoarthritis cartilage in vivo.

OBJECTIVES: This study aimed to explore the effects and relative mechanism of JMJD3 on knee osteoarthritis (OA). METHODS: In this study, we first analyzed the expression of JMJD3 in OA cartilage using western blot and immunohistochemistry. In an in vitro study, the effects of GSK-J4, JMJD3 inhibitor, on ATDC-5 chondrocytes were evaluated by CCK-8 assay. Real-time PCR and western blot were used to examine the inhibitory effect of GSK-J4 on the inflammation and ECM degradation of chondrocytes. NF-κB p65 phosphorylation and nuclear translocation were measured by western blot and immunofluorescence. In the animal study, twenty mice were randomized into four experimental groups: sham group, DMM-induced OA + DMSO group, OA + low-dose GSK-J4 group, and OA + high-dose GSK-J4 group. After the treatment, hematoxylin-eosin and safranin O/fast green staining were used to evaluate cartilage degradation of knee joint, with OARSI scores for quantitative assessment of cartilage damage. RESULTS: Our results revealed that JMJD3 was overexpressed in OA cartilage and GSK-J4 could suppress the IL-1ß-induced production of pro-inflammatory cytokines and catabolic enzymes, including IL-6, IL-8, MMP-9 and ADAMTS-5. Consistent with these findings, GSK-J4 could inhibit IL-1ß-induced degradation of collagen II and aggrecan. Mechanistically, GSK-J4 dramatically suppressed IL-1ß-stimulated NF-κB signal pathway activation. In vivo, GSK-J4 prevented cartilage damage in mouse DMM-induced OA model. CONCLUSIONS: This study elucidates the important role of JMJD3 in cartilage degeneration in OA, and our results indicate that JDJM3 may become a novel therapeutic target in OA therapy.

Minimally invasive plating for fresh displaced midshaft fractures of the clavicle.

The authors retrospectively reviewed 269 patients treated from September 2006 to August 2011 with the minimally invasive plate osteosynthesis (MIPO) technique using a universal reconstruction ribbon plate for fresh displaced midshaft fracture of the clavicle. Mean follow-up was 40.6 months. All had bony union (average healing time, 14.6 weeks). At 2-month postoperative follow-up, the mean Constant-Murley score was 92 points and the mean Disabilities of the Arm, Shoulder and Hand (DASH) score was 4.6 points. A total of 166 patients underwent hardware removal at an average of 15 months. A total of 258 patients were satisfied with the results of this surgery. This technique appears to be safe, simple, effective, and practical and to lead to rapid recovery, a high rate of union, a favorable cosmetic effect, and excellent function restoration. Thus, it can be considered an alternative to conventional plate osteosynthesis, intramedullary fixation, or non-operative treatment for fresh displaced midshaft clavicle fractures.