MiR-29a-3p mediates phosphatase and tensin homolog and inhibits osteoarthritis progression.

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.

Percutaneous kyphoplasty combined with pediculoplasty for the surgical treatment of osteoporotic thoracolumbar burst fractures.

OBJECTIVE: This study introduces a minimally invasive technique for efficient three-column reconstruction, augmentation, and stabilization of osteoporotic thoracolumbar burst fractures (OTLBFs). METHODS: Sixty-eight patients with OTLBFs and no neurological deficits were included from July 2019 to September 2020. The patients were divided into two groups: the simple percutaneous kyphoplasty (PKP) group (n = 32) and the percutaneous kyphoplasty combined with pediculoplasty (PKCPP) group (n = 36). The clinical and radiological outcomes were assessed during a minimum 1-year follow-up period. Clinical outcomes were assessed via the visual analog scale (VAS) and modified MacNab grading criteria. The radiological outcomes included the Cobb angle (CA), anterior wall height (AWH), and posterior wall height (PWH). The surgery duration, postoperative analgesic dosage, length of hospital stay, and complications were recorded. RESULTS: Surgery duration was not significantly different between the two groups (P > 0.05). The PKCPP group had a lower analgesic dosage and shorter hospital stay (P < 0.05). Postoperatively, the PKCPP group exhibited better VAS scores and modified MacNab scale scores (P < 0.05), but the differences at the last follow-up assessment were not significant (P > 0.05). Postoperative CA, AWH, and PWH correction were not significantly different on the first postoperative day (P > 0.05). However, the PKCPP group had significantly less CA and PWH loss of correction at the last follow-up visit (P < 0.05). The PKCPP group had significantly fewer complications (P < 0.05). CONCLUSIONS: The PKCPP technique complements simple PKP for OTLBFs. It quickly relieves pain, maintains the vertebral body height and Cobb angle, ensures cement stabilization, and offers more stable three-column support.

Identification of genes contributing to cisplatin resistance in osteosarcoma cells.

Osteosarcomas are prevalent in children and young adults and have a high recurrence rate. Cisplatin, doxorubicin, and methotrexate are common adjuvant chemotherapy drugs for treatment of osteosarcoma, but multidrug resistance is a growing problem. Therefore, understanding the molecular mechanisms of chemotherapy resistance in osteosarcoma cells is crucial for developing new therapeutic approaches and ultimately improving the prognosis of osteosarcoma patients. To identify genes associated with cisplatin resistance in osteosarcoma, we screened a large-scale mutant library generated by transfecting human osteosarcoma cells with a piggyBac (PB) transposon-based gene activation vector. Several candidate genes were identified by using Splinkerette-PCR paired with Next Generation Sequencing. We created a disease-free survival predictor model, which includes ZNF720, REEP3, CNNM2, and CGREF1, using TARGET (Therapeutically Applicable Research to Generate Effective Treatments) datasets. Additionally, the results of our enrichment analysis between the Four_genes_high group and Low_group suggested that these four genes may participate in cisplatin resistance in osteosarcoma through cross talk between various signaling pathways, especially the signaling pathway related to bone formation. These data may help guide future studies into chemotherapy for osteosarcoma.

Exosomes: A promising therapeutic strategy for intervertebral disc degeneration.

As a common problem all over the world, low back pain (LBP) places a huge social and economic burden on people. Intervertebral disc degeneration (IDD) is often considered to be the main cause of low back pain. The current methods of treating disc degenerative diseases mainly focus on relieving symptoms, including surgery and conservative treatment, but none of them can be treated with the etiology, which means that the normal structure of the intervertebral disc cannot be fundamentally restored. With the development of tissue engineering and regenerative medicine, exosomes from different sources, especially mesenchymal stem cell-derived exosomes (MSC-exos) as active biological substances for intercellular communication have made rapid progress due to their potency in promoting tissue regeneration. The study of exosomes in the field of treatment of IDD has yielded many surprising results. This paper mainly reviews the mechanism and function of exosomes in the study of delaying or reversing IDD, as well as gives the prospects and challenges of exosomes.

Histone demethylase KDM5A promotes tumorigenesis of osteosarcoma tumor.

Osteosarcoma is a primary bone malignancy with a high rate of recurrence and poorer prognosis. Therefore, it is of vital importance to explore novel prognostic molecular biomarkers and targets for more effective therapeutic approaches. Previous studies showed that histone demethylase KDM5A can increase the proliferation and metastasis of several cancers. However, the function of KDM5A in the carcinogenesis of osteosarcoma is not clear. In the current study, KDM5A was highly expressed in osteosarcoma than adjacent normal tissue. Knockdown of KDM5A suppressed osteosarcoma cell proliferation and induced apoptosis. Moreover, knockdown of KDM5A could increase the expression level of P27 (cell-cycle inhibitor) and decrease the expression of Cyclin D1. Furthermore, after knockout of KDM5A in osteosarcoma cells by CRISPR/Cas9 system, the tumor size and growth speed were inhibited in tumor-bearing nude mice. RNA-Seq of KDM5A-KO cells indicated that interferon, epithelial-mesenchymal transition (EMT), IL6/JAK/STAT3, and TNF-α/NF-κB pathway were likely involved in the regulation of osteosarcoma cell viability. Taken together, our research established a role of KDM5A in osteosarcoma tumorigenesis and progression.