Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an in vitro OA environment induced by interleukin-1 beta (IL-1β), melatonin treatment improved cell proliferation of human chondrocytes, promoted the expression of cartilage ECM proteins (e.g., type II collagen and aggrecan), and inhibited the levels of IL-1β-induced proteinases, such as matrix metalloproteinase 9 (MMP9), MMP13, ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), and ADAMTS5. Both the microarray and polymerase chain reaction (PCR) experiments revealed that miR-140 was a melatonin-responsive microRNA and melatonin upregulated miR-140 expression, which was suppressed by IL-1β stimulation. In vivo experiments demonstrated that intra-articular injection of melatonin prevented disruptions of cartilage matrix homeostasis and successfully alleviated the progression of surgery-induced OA in mice. Transfection of miR-140 antagomir completely counteracted the antiarthritic effects of melatonin by promoting matrix destruction. Our findings demonstrate that melatonin protects the articular cartilage from OA-induced degradation by targeting miR-140, and intra-articular administration of melatonin may benefit patients suffering from OA.
Background: This meta-analysis was designed to investigate the long-term efficacy and safety between cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) in treating cervical disc degenerative diseases (CDDDs). Methods: Literature search was performed on Pubmed, Embase, Cochrane Library, and Web of Science before Jan 2019. Surgical details, clinical outcomes, range of motion (ROM), complications, and reoperation rates between CDA and ACDF groups were compared and analyzed. A fixed-or random-effects model was applied based on different heterogeneity. STATA (Version 11.0) software was used to perform data analysis. Results: A total of 13 randomized controlled trial studies with more than 60 months of follow-up (mean 83.1 months) were enrolled in this meta-analysis. Pool results indicated that the CDA group exhibited significantly better outcomes in clinical scores (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.15-2.08, p = 0.004) and preservation of ROM (mean difference = 1.77, 95% CI: 1.60-1.95, p < 0.001) than the ACDF group. Meanwhile, the incidence of adjacent segment disease (ASD) (OR = 0.51, 95% CI: 0.35-0.76, p = 0.001) and occurrence of reoperation (OR = 0.41, 95% CI: 0.25-0.69, p = 0.001) were lower in the CDA group than in the ACDF group.
Percutaneous vertebral augmentation (Percutaneous vertebroplasty, PVP and Percutaeous kyphoplasty, PKP) for the treatment of metastatic spinal lesions has been considered as a preferred alternative to relieve pain and rebuild spinal stabilization relying on minimally invasive procedure. However, there have been few reports on clinical outcomes of percutaneous kyphoplasty in the treatment of osteolytic and osteoblastic metastatic vertebral fracture. We report our experience for 81 kyphoplasty procedures performed in 45 patients with thoracic and lumbar vertebral lesions caused by metastases. 4 out of the 45 patients were withdrawn at 1-year follow-up. 41 patients demonstrated good clinical result. The osteoblastic group performed a better pain relief in visual analog scale (VAS) score after the treatment than the osteoclastic group 3 days, 1 month, 3 months and 1 year after the KP. And the Oswestry Disability Index (ODI) scores of the osteoblastic group is lower than that of the osteoclastic group just in 3 days after the KP. And there were no significant difference between the two groups of ODI scores 1 month, 3 month and 1 year after the KP. And there were no statistical differences of the radiographic parameters including VB height variation and local kyphosis angle (LKA) between the two groups. Kyphoplasty results in an effective, minimally invasive procedure for the stabilization of thoracic and lumbar metastatic vertebral lesions, including both osteoblastic and osteoclastic types, which achieves statistically significant pain relief, function improvement, preventing further local kyphotic deformity, and VB height.
Yes-associated protein (YAP) and extracellular signal-regulated kinase (ERK) have been considered as key regulators in tissue homeostasis, organ development, and tumor formation. However, the roles of YAP and ERK in the mediating strain mechanosensing in the growth plate cartilage have not been determined. In this study, chondrocytes obtained from the growth plate cartilage of 2-week-old Sprague-Dawley rats were subjected to the mechanical strain with different magnitudes and durations at a frequency of 0.5 Hz. We found that YAP and ERK activation in response to mechanical strain was time and magnitude dependent. Pretreatment with a RhoA inhibitor (C3 toxin) or a microfilament cytoskeleton disrupting reagent (cytochalasin D) could suppress their activation. In addition, activated YAP and ERK were able to induce cell cycle progression by up-regulating the expression of cell cycle-related genes. These results shed new light on the function of YAP and ERK in mechanical strain-promoted growth plate development. Our results also provided evidence that RhoA and cytoskeletal dynamics are required for this mechanotransduction. ß
The volume of blood loss was lower and the operation time was shorter in ACDF than in ACCF for the treatment of two-level CSM. Sagittal balance was better in the ACDF group than in the ACCF group, and this observation may lead to a reduced occurrence of axial symptoms.
Objective. To investigate the change of spinopelvic sagittal balance and clinical outcomes after posterior lumbar interbody fusion (PLIF) in patients with degenerative spondylolisthesis (DS), especially the relationship between sagittal spinopelvic parameters and persistent low back pain (PLBP). Methods. 107 patients who were diagnosed with DS and underwent PLIF in our department were enrolled retrospectively in the present study. Sagittal spinopelvic parameters including lumbar lordosis (LL), segmental lordosis (SL), height of the disc (HOD), sacral slope (SS), pelvic incidence (PI), and pelvic tilt (PT) were recorded pre- and postoperatively. Sagittal balance and clinical outcomes were compared between patients with and without PLBP. Pearson correlation was used to analyze the change of sagittal balance parameters and clinical functions. Logistic regression analysis was performed to examine the risk factors of PLBP. Results. It showed significant improvements of SL, HOD, and PT postoperatively. Both the Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI) had significant improvement postoperatively. Change of PT and SL also differed observably between patients with and without PLBP. SL and PT were correlated with NRS and ODI, and insufficient restoration of PT was an independent factor for PLBP. Conclusion. The sagittal balance parameters and clinical outcomes can be improved markedly via PLIF for treating DS. Restoration of SL and PT was correlated with satisfactory outcomes, and adequate improvement of PT may have positive impact on reducing PLBP.
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