MicroRNA-410-3p modulates chondrocyte apoptosis and inflammation by targeting high mobility group box 1 (HMGB1) in an osteoarthritis mouse model.

BACKGROUND: Osteoarthritis (OA) is the most prevalent type of arthritis, which commonly involves inflammation in the articular cartilage in OA pathogenesis. MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various diseases including OA. MiR-410-3p has been demonstrated to mediate inflammatory pathways, however, the regulatory functions of miR-410-3p in OA remain largely unknown. METHODS: The regulations of miR-410-3p were investigated in OA. Mouse primary chondrocytes and mouse in vivo models were used. The expression levels of miR-410-3p and HMGB1 were measured by qPCR. The transcription activity of NF-κB was assessed by luciferase reporter assay. MTT assay was performed to assess cellular proliferation. Cell apoptosis was evaluated with the Fluorescein Isothiocyanate (FITC) Annexin V assay. Expression levels of proteins were determined by Western blot. RESULTS: The results demonstrated that miR-410-3p was markedly downregulated in articular cartilage tissues as well as in lipopolysaccharide (LPS)-treated chondrocytes in OA mice. In addition, upregulation of miR-410-3p markedly inhibited LPS-induced apoptosis of chondrocytes. The results also demonstrated that the high mobility group box 1 (HMGB1) was a target of miR-410-3p. LPS-induced upregulated expression of HMGB1 significantly suppressed expression of miR-410-3p. Furthermore, upregulation of miR-410-3p markedly inhibited HMGB1 expression, the nuclear factor (NF)-kB activity and pro-inflammatory cytokines production. Taken together, the results suggested that miR-410-3p targeted HMGB1 and modulated chondrocytes apoptosis and inflammation through the NF-κB signaling pathway. CONCLUSIONS: These findings provide insights into the potential of miR-410-3p/ HMGB1 as therapeutic targets for OA treatment.

[Observation of stand-alone MC+polyether-ether-ketone (PEEK) Cage in anterior cervical double-level fusion for more than 2 years follow-up].

OBJECTIVE: To investigate the effectiveness of stand-alone MC+polyether-ether-ketone (PEEK) Cage (single blade type) in anterior cervical double-level fusion for more than 2 years follow-up. METHODS: A clinical data of 30 patients who were treated with anterior cervical fusion surgery with stand-alone MC+PEEK Cage (single blade type) between January 2013 and December 2016 and followed up for more than 2 years, was retrospectively analyzed. There were 16 males and 14 females, aged from 34 to 72 years with an average of 52.2 years. There were 16 cases of cervical spondylotic myelopathy, 8 cases of cervical spondylotic myelopathy, and 6 cases of traumatic cervical disc herniation. The continuous double segments were C 4, 5, C 5, 6 in 12 cases and C 5, 6, C 6, 7 in 18 cases; and the disease duration ranged from3 days to 24 months (mean, 12 months). Postoperative neck hematoma and wound healing were observed; dysphagia was assessed by Bazaz system; and bone fusion was assessed by Suk method. Before operation, at 1 week after operation, and at last follow-up, the Japanese Orthopaedic Association (JOA) score was used to evaluate the neurological recovery; the cervical X-ray film was performed to record the cervical curvature (C 2-C 7 Cobb angle), the height of the intervertebral space of the fusion segment, and to judge the occurrence of the fusion Cage subsidence. RESULTS: No complication such as neck hematoma, incision infection, or esophageal fistula was found, primary healing of incisions was obtained in all cases. All patients were followed up 24-72 months (mean, 46 months). Neurological symptoms such as limb numbness and pain gradually disappeared after operation; during the follow-up period, the cervical curvature could be effectively maintained; dysphagia and internal fixation related complications such as displacement of Cages were not found. All patients obtained bony fusion from 3 to 8 months with an average time of 4.3 months. Compared with preoperative ones, the JOA score, intervertebral space height, and Cobb angle of cervical spine were significantly improved at 1 week after operation and at last follow-up ( P<0.05), but there was no significant difference between 1 week after operation and last follow-up ( P>0.05). CONCLUSION: The application of stand-alone MC+PEEK Cage (single card type) in anterior cervical fusion can provide early cervical stability, effectively maintain the physiological curvature of cervical spine and the height of fusion intervertebral space.

[Clinical application of stand-alone MC+PEEK cage in the anterior cervical fusion].

OBJECTIVE: To explore the effect of clinical application of stand-alone MC+PEEK cage in anterior cervical fusion. METHODS: From January 2011 to January 2014,50 patients were treated with the MC+PEEK cage filled with autogenous cancellous illic-bone graft after anterior cervical discectomy. There were 22 patients with cervical spondylosis,26 patients with traumatic cervical disc herniation, 2 patients with cervical instability in these patients. There were 32 males and 18 females, aged from 30 to 79 years old with an average of 53.30 years old. There were 32 patients with single segment, 15 patients with double segments and 3 patients with three segments. Cervical AP and lateral and the flexion-extension X-rays were regularly taken in order to assess the cervical physiological curvature, the graft fusion and internal fixation related complications. Nerve function, clinical effect and bone fusion were respectively evaluated according to Japan Orthopedic Association (JOA), Otani grade and Suk method. RESULTS: All patients were followed up from 6 to 36 months with an average of 20 months. No correlated surgical complications were found and all patients obtained bony fusion with an average time of 4.30 months. JOA score had significantly improvement after surgery (P < 0.05). The JOA score was 10.60 ± 3.00 before surgery and 16.10 ± 2.20, 16.40 ± 2.35 at one week and six months after surgery respectively. According to Otani grade,40 cases got excellent results, 9 good, 1 fair. No significant dysphagia and internal fixation related complications such as displacement of cages were found during the follow-up period. CONCLUSION: Using this cage in anterior cervical fusion can obtain satisfactory clinical effect with less operation injury and reduce the complications. It is a better fusion method in anterior cervical fusion.