Neferine alleviates ovariectomy-induced osteoporosis by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells via regulation of the p38MAPK pathway.

OBJECTIVE: Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. METHODS: We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. RESULTS: Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. CONCLUSION: Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.

miR-3195 suppresses the malignant progression of osteosarcoma cells via targeting SOX4.

BACKGROUND: Osteosarcoma (OS) is a highly invasive primary malignancy of the bone that is common in children and adolescents. MicroRNAs (miRNAs) are novel diagnostic and predictive biomarkers for cancers. The miRNA miR-3195 is aberrantly expressed in multiple types of tumors. However, the expression levels and biological functions of miR-3195 in OS remain unclear. METHODS: Two Gene Expression Omnibus (GEO) datasets (GSE69470 and GSE16088) were used to analyze differentially expressed miRNAs and mRNAs in osteosarcoma cell lines and OS tissues. Quantitative RT-PCR was used to detect the expression levels of miR-3195 and the SRY-box transcription factor 4 (SOX4) mRNA in OS tissues and cell lines. The relationship between miR-3195 and the 3'-upstream region (3'-UTR) in the SOX4 mRNA (predicted through bioinformatics) was analyzed using Pearson's correlation analysis and confirmed by a dual-luciferase reporter gene experiment. Cell counting kit-8 assays, colony formation assays, flow cytometry, wound healing assays, transwell assays, and western blotting were performed to explore the effects of miR-3195 levels on SOX4 affected OS cell biological behavior. RESULTS: Our results revealed that miR-3195 was the most down-regulated miRNA and SOX4 was the most up-regulated mRNA by Bioinformatic analysis. It was further confirmed miR-3195 had low expression, and SOX4 had high expression levels in clinical OS tissue samples; the expression levels of both genes were negatively correlated with each other in OS tissues. Overexpression of miR-3195 in OS cell lines significantly inhibited cell proliferation, migration, and invasiveness, while promoting apoptosis; all these effects were reversed by increasing SOX4 expression levels. We also found that miR-3195 could directly bind with the SOX4 gene and down-regulate SOX4 expression. CONCLUSIONS: miR-3195 can modulate proliferation, migration, invasiveness, and apoptosis in OS cells by regulating the SOX4 gene. Thus, the miR-3195/SOX4 signaling may be a novel therapeutic target in OS treatment.

Long non-coding RNA SOX21-AS1: A potential tumor oncogene in human cancers.

Emerging data have proposed that the aberrant level of long noncoding RNAs (lncRNA) is related to the onset and progression of cancer. Among them, lncRNA SOX21-AS1 was shown to upregulate and seem to be a novel oncogene in various cancer, including ovarian cancer, lung cancer, breast cancer, pancreatic cancer, osteosarcoma, and melanoma. Available data indicated that SRY-box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1) mostly acts as a competing endogenous RNA (ceRNA) to inhibit the level of its target microRNAs (miRNAs), leading to upregulation of their targets. In addition, SOX21-AS1 is engaged in various signaling pathways like transforming growth factor-ß (TGF-ß) signaling, Wnt signaling, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling. Moreover, this lncRNA was revealed to be correlated with the clinicopathological features of affected patients. SOX21-AS1 was also proved to enhance the resistance of ovarian cancer cells to cisplatin chemotherapy. SOX21-AS1 is markedly associated with poor prognosis and low survival of patients, proposing that it may be a prognostic and diagnostic biomarker in cancer. Overexpression of SOX21-AS1 is related to various cancer-related pathways, like epithelial mesenchymal transition (EMT), invasion, migration, apoptosis, and cell cycle arrest. In this work, we aimed to discuss the biogenesis, function, and underlying molecular mechanism of SOX21-AS1 in cancer progression as well as its potential as a prognostic and diagnostic biomarker in human cancers.

Screening and identification of susceptibility genes for osteosarcoma based on bioinformatics analysis.

Background: Gene play an important role in malignant tumors. However, there is still insufficient research on genetic variations in osteosarcoma (OS) patients. Therefore, we aimed to analyze the gene expression profile of OS using bioinformatics and to explore the pathogenesis of OS at the molecular level. Methods: The gene chip dataset of OS samples was downloaded from the Gene Expression Omnibus (GEO) database for screening differentially expressed genes (DEGs). The R language clusterProfiler software package was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs. The central node proteins of the protein interaction network were analyzed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Cytoscape, and its plug-ins cytoHubba and NetworkAnalyzer to find the key genes. Results: A total of 631 DEGs were obtained, including 362 upregulated genes and 269 downregulated genes. DEGs were mainly involved in the regulation of leukocyte chemotaxis and migration, vascular development, and other biological processes (BPs); mediation of receptor ligand activity, growth factor binding, growth factor activity, integrin binding, and other molecular functions (MFs); and were enriched in the extracellular matrix (ECM). Conclusions: DEGs in the ECM and growth factors play a key role in the development of OS. The leukocyte transendothelial migration pathway and the PI3K-AKT pathway are closely related to OS, and the related molecular mechanism is worthy of further study.

Anatomical changes in lumbosacral vertebrae and their correlation with facet joint-derived low back pain in patients with hip osteoarthritis after total hip arthroplasty: a cohort study.

Background: Little is known about the anatomical changes in lumbosacral vertebrae and their correlation with facet joint-derived low back pain in patients with hip osteoarthritis (HOA) after total hip arthroplasty. Methods: Seventy-four HOA patients with low back pain who underwent initial total hip arthroplasty were included. Their Harris Hip Score (HHS), Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) and anatomical parameters were analyzed. Paired t-tests were used to compare the various index scores before and after surgery, and independent sample t-tests were used for the between-group comparisons. Results: The HHS and ODI significantly changed at 3 and 6 months postoperatively [HHS: preoperative (43.56±4.34) vs. 3 months (80.34±5.23) vs. 6 months (84.37±4.78); ODI: preoperative (36.26±5.34) vs. 3 months (26.44±3.23) vs. 6 months (19.34±3.27); P<0.001]. At the first 3 months after surgery, the VAS low back pain score decreased from 5.24±1.21 to 2.89±1.03 (P<0.001), and the VAS hip pain score decreased from 7.45±1.32 to 2.34±1.12 (P<0.001). There was also a statistically significant difference between the preoperative and 1-month postoperative anatomical indices: lumbar lordosis (LL) increased significantly after surgery [preoperative (43.46°±13.89°) vs. 1 month (48.27°±14.42°), P=0.001], while slip angle (SA) decreased significantly [preoperative (89.20°±5.03°) vs. 1 month (84.45°±4.89°), P=0.010]. Sacral slope (SS) and radial abduction angle (RAA) showed significant postoperative changes compared with preoperative assessments; after surgery, SS increased significantly [preoperative (31.33°±8.23°) vs. 1 month (37.65°±8.19°), P=0.006), while RAA decreased significantly [preoperative (42.32°±8.12°) vs. 1 month (35.45°±7.67°), P=0.021]. Moreover, the increase of LL was both significantly correlated with the decrease of the VAS low back pain (P=0.009) and the VAS hip pain score (P=0.038). Conclusions: Total hip arthroplasty was associated with the anatomical changes in lumbosacral vertebrae.

[Effect of minimally invasive plate osteosynthesis through two approaches on bone metabolic activity and radial nerve injury in patients with humeral midshaft fracture].

OBJECTIVE: To compare application of minimally invasive plate osteosynthesis (MIPO) through two approaches for patients with humeral midshaft fracture, and analyzes the effect on bone metabolic activity and radial nerve injury. METHODS: From April 2014 to May 2017, 76 patients with humeral midshaft fracture treated by MIPO were selected and randomly divided into group A (anterior approache group) and group B (lateral approach group) according to random number stable. In group A, there were 38 patients including 22 males and 16 females, aged from 18 to 74 years old with an average age of(48.21±5.79) years old; 24 patients were caused by traffic accidents, 6 patients were caused by heavy object crushing, 8 patients were caused by falling down; 20 patient were on the right side, 18 patients were on the left side; 15 patients were type A, 17 patients were type B, 6 patients were type C according to AO classification; the patients were treated by MIPO through anterior approach. In group B, there were 38 patients including 23 males and 15 females, aged from 20 to 73 years old with an average age of(48.40±5.81) years old; 26 patients were caused by traffic accidents, 5 patients were caused by heavy object crushing, 7 patients were caused by falling down; 17 patients were on the right side, 21 patients were on the left side; 15 patients were type A, 18 cases were type B, 5 cases were type C according to AO classification; the patients were treated by MIPO through lateral approach. Intraoperative blood loss, operative time, hospital stays, fracture healing time between two groups were compared. Bone gla protein (BGP), collagen C-terminal peptide (CTX) and osteoprotegerin (OPG) were tested before and after operation. The incidence of radial nerve injury after operation was observed. RESULTS: All patients were followed-up from 12 to 18 months with an average of (15.4±2.1) months. There were no statistical differences in operative time, intraoperative blood loss between two groups. Hospital stays, fracture healing time in group A were(6.52±1.81) d, (13.27±3.01) weeks respectively, while in group B were(9.61±1.99) d, (14.83±3.08) weeks; and had differences between two groups. There were no differences in BGP, OPG and CTX, BGP between two groups and OPG in group A at 1 month after operation were(7.10±0.58) ng/ml, (173.67±9.12) pg/ml and higher than that of group B(6.63±0.62) ng/ml, (152.80±9.23) pg/ml; while CTX in group A (224.52±12.67) µg/ml was lower than that of group B(259.13±13.54) µg/ml(P<0.05). No patient occurred radial nerve injury in group A, 4 patients occurred radial nerve injury in group B, and had statistical differences between two groups(χ²=4.220, P<0.05). CONCLUSIONS: Compared with lateral approach, anterior approach has much more effective in minimally invasive MIPO for humeral shaft fractures, which could improve bone metabolism and reduce risk of radial nerve injury.

Risk Factors for Poor Prognosis of Cervical Spinal Cord Injury with Subaxial Cervical Spine Fracture-Dislocation After Surgical Treatment: A CONSORT Study.

BACKGROUND The objective of the study was to identify risk factors for poor prognosis of cervical spinal cord injury (SCI) with subaxial cervical fracture-dislocation after surgical treatment. MATERIAL AND METHODS A total of 60 cervical SCI patients with subaxial cervical fracture-dislocation were primarily included in the study from April 2013 to April 2018. All the enrolled subjects received surgical treatment. The enrolled patients with complete follow-up record were divided into 2 groups based on the neural function prognosis: a non-functional restoration group and a functional restoration group. Multivariate regression analysis was performed to identify independent risk factors for poor prognosis of SCI after surgical treatment. RESULTS Fifty-five subjects were included in this study, and the follow-up time ranged from 8.5 to 44.5 months. A total of 25 subjects were categorized into the non-functional restoration group and 30 subjects into the functional restoration group. According to the results of multivariate regression analysis, time from injury to operation (more than 3.8 days), subaxial cervical injury classification (SLIC, score more than 7.5), and maximum spinal cord compression (MSCC, more than 55.8%) are independent risk factors for poor prognosis of SCI after surgical treatment (p<0.05), with AUCs of 0.95 (time from injury to operation), 0.91 (SLIC score), and 0.96 (MSCC). CONCLUSIONS Time from injury to operation (more than 3.8 days), SLIC score (more than 7.5), and MSCC (more than 55.8%) are independent risk factors for poor prognosis of SCI with subaxial cervical fracture-dislocation after surgical treatment.