Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times. Functional studies demonstrated that overexpression of TRIM14 enhances osteosarcoma cell proliferation, clone formation, cell cycle procession, migration and invasion in vitro and promotes tumor growth in vivo, and conversely, its silencing has the opposite effects. Furthermore, TRIM14 overexpression induced activation of the AKT pathway. Inhibition of AKT expression reversed the TRIM14-mediated promotory effects on cell growth and mobility, in addition to TRIM14-induced epithelial-to-mesenchymal transition (EMT) and cyclin D1 upregulation. Our findings collectively suggest that TRIM14 functions as an oncogene by upregulating the AKT signaling pathway in osteosarcoma cells, supporting its potential utility as a therapeutic target for this disease.

Background/Aims: Human bone marrow-derived mesenchymal stem cells (hMSCs) are a promising cell source for bone engineering owing to their high potential to differentiate into osteoblasts. The bone morphogenetic protein-inducible gene homeobox a10 (HOXA10) is a critical regulator of osteogenesis. The objective of the present study was to identify microR-NAs (miRNAs) targeting HOXA10 and examine the effects on the osteogenic differentiation of hMSCs. Methods: Based on in silico analysis, HOXA10-targeting miRNAs were selected and their regulatory roles in osteoblast differentiation were investigated. Results: Six HOXA10-targeting miRNAs were identifIed by computational analysis, of which miR-320a was selected for further analysis because it was downregulated during osteogenic induction. Overexpression of miR-320a downregulated HOXA10 and significantly inhibited osteogenesis in hMSCs, as determined by the downregulation of the osteogenic markers Runx2, ALP, and OC and the inhibition of ALP activity and matrix mineralization, whereas miR-320a inhibition had the opposite effects. Furthermore, ectopic expression of HOXA10 (not including 3′-UTR) rescued the effects of miR-320a on osteogenic differentiation. Conclusion: These results suggest that miR-320a acts as a critical regulator of osteogenic differentiation of hMSCs by repressing its target HOXA10.

Mounting evidence indicates that microRNAs (miRNAs) are involved in multiple processes of osteogenic differentiation. MicroRNA-101 (miR-101), identified as a tumor suppressor, has been implicated in the pathogenesis of several types of cancer. However, the expression of miR-101 and its roles in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) remain unclear. We found that the miR-101 expression level was significantly increased during the osteogenic differentiation of hBMSCs. MiR-101 depletion suppressed osteogenic differentiation, whereas the overexpression of miR-101 was sufficient to promote this process. We further demonstrated that enhancer of zeste homolog 2 (EZH2) was a target gene of miR-101. EZH2 overexpression and depletion reversed the promoting or suppressing effect of osteogenic differentiation of hBMSCs, respectively, caused by miR-101. In addition, we showed that miR-101 overexpression promoted the expression of Wnt genes, resulting in the activation of the Wnt/β-catenin signaling pathway by targeting EZH2, while the activity of β-catenin and the Wnt/β-catenin signaling pathway was inhibited by ICG-001, a β-Catenin inhibitor, which reversed the promoting effect of miR-101. Finally, miR-101 also promotes in vivo bone formation by hBMSCs. Collectively, these data suggest that miR-101 is induced by osteogenic stimuli and promotes osteogenic differentiation at least partly by targeting the EZH2/Wnt/β-Catenin signaling pathway.

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We review the literature and discuss the functional anatomy of spinal cord of BSS combined with HS. And it is important that clinicians be aware that a MRI of spinal cord is needed for those patients with a thoracic sensory level, and that a thoracic sensory level might not only depend on the level of spinal cord injury but also on the stage of evolution of the lesion.

Background New-onset neurological symptoms such as numbness and pain in lower extremities might appear immediately after conventional lumbar interbody fusion (LIF) surgery performed in patients with lumbar spinal stenosis. Methods and Analysis: This is a multicenter, randomized, open-label, parallel-group, active-controlled trial investigating the clinical outcomes of modified LIF sequence versus conventional LIF sequence in treating patients with lumbar spinal stenosis. A total of 254 eligible patients will be enrolled and randomized in a 1:1 ratio to either modified LIF sequence or conventional LIF sequence group. The primary outcome measure is the perioperative incidence of new-onset lower extremity neurological symptoms, including new adverse events of pain, numbness, and foot drop of any severity. Important secondary endpoints include visual analogue scale (VAS) pain score and lumbar Japanese Orthopaedic Association (JOA) recovery rate. Other safety endpoints will also be evaluated. The safety set used for safety data analysis by the actual surgical treatment received and the full analysis set for baseline and efficacy data analyses according to the intent-to-treat principle will be established as the two analysis population in the study. Conclusion This study is designed to investigate the clinical outcomes of modified LIF sequence in patients with lumbar spinal stenosis. It aims to provide clinical evidence that the modified “fixation-fusion” sequence of LIF surgery is effective in treating lumbar spinal stenosis. (Words: 221) Trial registration: http://www.chictr.org.cn/index.aspx ID: ChiCTR2100048507

Background: Calcification of the cervical ligamentum flavum(CLF) and periodontoid calcification are two rare diseases in the orthopaedic clinic. Only few reports have described these coexisting conditions. Objectives: We present our cases of cervical radiculomyelopathy caused by CLF combined with or without periodontoid calcification, and the relationship between the two clinical conditions are briefly discussed on the review of data of the literature. Methods: We retrospectively reviewed 33 patients with CLF. In our case series, the clinical and radiological characteristics of patients are described and analyzed. The calcification surrounding the dens is termed as crowned dens sign(CDSign) in our study. And the relationship between the two conditions of CLF and CDSign are discussed. Results:There were 28 women and 5 men aged between 56 and 86 years. Neurological symptoms and neck pain were presented in most patients. Calcification sites on axial CT images were described in 33 cases with 81 levels, C4-5 and C5-6 were attacked most frequently, and multiple- rather than single-level involvement could be observed in our series. CDSign was identified in 26 cases, and the the prevalence were 79%. Following evaluation, 23 patients received posterior surgery, and 8 patients underwent anterior cervical surgery. Conclusions: The coexistence of CDSign and CLF is an uncommon phenomenon. The association of these two diseases is stronger than a coincidence. It is possible that the coexistence of CLF with CDSign may be a rare form of the cervical manifestation of calcium pyrophosphate dihydrate (CPPD) deposition disease.