Surgical treatment of thoracolumbar fracture with incomplete lower limb paralysis in a patient with COVID-19.

Since December 2019, COVID-19, an acute infectious disease, has gradually become a global threat. We report a case of thoracolumbar fractures (T12 and L1) and incomplete lower limb paralysis in a patient with COVID-19. After a series of conservative treatment which did not work at all, posterior open reduction and pedicle screw internal fixation of the thoracolumbar fracture were performed in Wuhan Union Hospital. Three weeks later, the patient could stand up and the pneumonia is almost cured. We successfully performed a surgery in a COVID-19 patient, and to our knowledge it is the first operation for a COVID-19 patient ever reported.

Outcome of segmental prosthesis reconstruction for diaphyseal bone tumors: a multi-center retrospective study.

BACKGROUND: The optimal reconstructive method after diaphyseal malignant bone tumor resection remains controversial. This multicenter clinical study was designed to investigate the clinical value and complications of segmental prosthesis in the repair of diaphyseal defects. METHODS: We present 49 patients from three clinical centers treated with wide resection for primary or metastatic bone tumors involving the diaphysis of the femur, tibia, humerus, or ulna, followed by reconstruction using a modular intramedullary segmental prosthesis. RESULTS: Enrolled patients included 23 men and 26 women with a mean age of 63.3 years. Of these, seven patients had primary bone tumors and 42 patients had metastatic lesions. At the mean follow-up of 13.7 months, 17 patients were alive, 31 patients were deceased due to tumor progression, and one patient was dead of another reason. There were eight nononcologic complications (two with radial nerve injury, three with delayed incision healing, two with aseptic loosening in the proximal humerus prosthetic stem and one with structural failure) and three oncologic complications (three with primary tumor recurrence) among all patients. The incidence of complications in primary tumor patients (4/7, 57.1%) was higher than that in patients with metastatic tumors (7/42, 16.7%) (p = 0.036). Aseptic loosening and mechanical complications were not common for patients with primary tumors, although the reconstruction length difference was statistically significant (p = 0.023). No statistically significant differences were observed in limb function, while the mean musculoskeletal tumor society score was 21.2 in femora, 19.6 in humeri, and 17.8 in tibiae (p = 0.134). CONCLUSIONS: Segmental prostheses represent an optional method for the reconstruction of diaphyseal defects in patients with limited life expectancy. Segmental prostheses in the humerus experienced more complications than those used to treat lesions in the femur.

Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF.

Compression-induced programmed cell death of nucleus pulposus (NP) cells is an important contributor to intervertebral disc degeneration (IDD). Dynamin-related protein 1 (Drp1), a crucial mitochondrial fission protein, triggers programmed necrosis upon cellular injury. However, limited information is available about the role of Drp1 in compression-induced programmed necrosis of NP cells. In the present study, we found that compression resulted in upregulation and mitochondrial translocation of Drp1. Inhibition of Drp1 by siRNA or mitochondrial division inhibitor 1 (mdivi-1) effectively prevented the programmed necrosis of NP cells treated with compression. Furthermore, Drp1 promoted mitochondrial translocation of p53 and nuclear translocation of apoptosis-inducing factor (AIF) in compression-treated NP cells. Inhibition of p53 mitochondrial translocation by pifithrin-µ (PFT-µ) and silencing of AIF expression by siRNA significantly alleviated compression-induced NP cell programmed necrosis. These data indicates that Drp1 mediates compression-induced programmed necrosis of NP cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF.

Effect of microRNA-101 on proliferation and apoptosis of human osteosarcoma cells by targeting mTOR.

Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.

Cell death in intervertebral disc degeneration.

Degeneration of intervertebral disc (IVD) is mainly a chronic process of excessive destruction of the extracellular matrix (ECM), and also is thought to be the primary cause of low back pain. Presently, however, the underlying mechanism of IVD degeneration is still not elucidated. Cellular loss from cell death has been believed to contribute to the degradation of ECM and plays an important role in the process of IVD degeneration, but the mechanisms of cell death in degenerated IVD remain unclear. Apoptosis, a very important type of IVD cell death, has been considered to play a crucial role in the process of degeneration. Autophagy, a non-apoptosis death type of programmed cell death, has been considered extensively involved in many pathological and physiological processes, including the degenerative diseases. Thus, the research on cell death in IVD degeneration has become a new focus recently. In this review, by analyzing the available literature pertaining to cell death in IVD and discussing the inducing factors of IVD degeneration, NP cells and ECM in IVD degeneration, apoptotic signal transduction pathways involved in IVD cell death, the relationship of cell death with IVD degeneration and potential therapeutic strategy for IVD degeneration by regulating cell death, we conclude that different stimuli induce cell death in IVD via various signal transduction pathways, and that cell death may play a key role in the degenerative process of IVD. Regulation of cell death could be a potential and attractive therapeutic strategy for IVD degeneration.

Construction of self-assembled cartilage tissue from bone marrow mesenchymal stem cells induced by hypoxia combined with GDF-5.

It is widely known that hypoxia can promote chondrogenesis of human bone marrow derived mesenchymal stem cells (hMSCs) in monolayer cultures. However, the direct impact of oxygen tension on hMSC differentiation in three-dimensional cultures is still unknown. This research was designed to observe the direct impact of oxygen tension on the ability of hMSCs to "self assemble" into tissue-engineered cartilage constructs. hMSCs were cultured in chondrogenic medium (CM) containing 100 ng/mL growth differentiation factor 5 (GDF-5) at 5% (hypoxia) and 21% (normoxia) O2 levels in monolayer cultures for 3 weeks. After differentiation, the cells were digested and employed in a self-assembly process to produce tissue-engineered constructs under hypoxic and normoxic conditions in vitro. The aggrecan and type II collagen expression, and type X collagen in the self-assembled constructs were assessed by using immunofluorescent and immunochemical staining respectively. The methods of dimethylmethylene blue (DMMB), hydroxyproline and PicoGreen were used to measure the total collagen content, glycosaminoglycan (GAG) content and the number of viable cells in each construct, respectively. The expression of type II collagen and aggrecan under hypoxic conditions was increased significantly as compared with that under normoxic conditions. In contrast, type X collagen expression was down-regulated in the hypoxic group. Moreover, the constructs in hypoxic group showed more significantly increased total collagen and GAG than in normoxic group, which were more close to those of the natural cartilage. These findings demonstrated that hypoxia enhanced chondrogenesis of in vitro, scaffold-free, tissue-engineered constructs generated using hMSCs induced by GDF-5. In hypoxic environments, the self-assembled constructs have a Thistological appearance and biochemical parameters similar to those of the natural cartilage.

Clinical analysis of 73 cases of intraspinal nerve sheath tumor.

Seventy-three patients with spinal nerve sheath tumor who were surgically treated in our hospital during the years 2004-2010 were retrospectively reviewed with respect to recovery of neurological function, recurrence of the tumor and occurrence of kyphotic deformities. Preoperative clinical manifestations, imaging data, surgical records and follow-up results were comprehensively analyzed. The follow-up duration was 12-60 months with an average of 32.0 months. Out of the 73 cases enrolled, 69 had gradual recovery of sensation, motor and sphincter functions 1 week to 3 months after operation. Forty-six cases had incomplete paralysis, whose American Spinal Injury Association (ASIA) grades, however, were gradually increased during the follow-up period, 4 cases had no significant improvement of the clinical symptoms and no change in ASIA grades during the follow-up period. Two cases had postoperative recurrence of the tumor. There were no deaths, no spinal instability, and no kyphotic malformations found in any cases. Our study indicated that complete removal of the tumor is important for good recovery, and an ideal surgical method may reduce the recurrence of the tumor or the occurrence of complications.

Promotion of chondrogenesis of marrow stromal stem cells by TGF-ß3 fusion protein in vivo. [corrected].

The purpose of this study was to investigate the repair of the osteoarthritis(OA)-induced cartilage injury by transfecting the new TGF-ß3 fusion protein (LAP-MMP-mTGF-ß3) with targeted therapy function into the bone marrow-derived mesenchymal stem cells (MSCs) in rats. The recombinant of pIRES-EGFP-MMP was constructed by combination of DNA encoding MMP enzyme cutting site and eukaryotic expression vector pIRES-EGFP. LAP and mTGF-ß3 fragments were obtained from rat embryos by RT-PCR and inserted into the upstream and downstream of MMP from pIRES-EGFP-MMP respectively, so as to construct the recombinant plasmid of pIRES-EGFP-LAP-MMP-mTGF-ß3. pIRES-EGFP-LAP-MMP-mTGF-ß3 was transfected into rat MSCs. The genetically modified MSCs were cultured in medium with MMP-1 or not. The transfected MSCs were transplanted in the rat OA models. The OA animal models were surgically induced by anterior cruciate ligament transaction (ACLT). The pathological changes were observed under a microscope by HE staining, Alcian blue, Safranin-fast Green and graded by Mankin's scale. pIRES-EGFP-LAP-MMP-mTGF-ß3 was successfully constructed by means of enzyme cutting and sequencing, and the mTGF-ß3 fusion protein (39 kD) was certified by Western blotting. Those genetically modified MSCs could differentiate into chondrocytes induced by MMP and secrete the relevant-matrix. The transfected MSCs could promote chondrogenesis and matrix production in rat OA models in vivo. It was concluded that a new fusion protein LAP-MMP-mTGF-ß3 was constructed successfully by gene engineering, and could be used to repair the OA-induced cartilage injury.

Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells.

Various mechanical stresses can induce apoptosis of nucleus pulposus (NP) cells and intervertebral disc (IVD) degeneration in vivo, but the underlying molecular mechanism by which the number of NP cells is decreased in degenerated IVD is still not elucidated. The purpose of this study was to investigate whether the mitochondrial pathway is involved in compression-induced apoptosis of rabbit NP cells. The compression apparatus was used to investigate the effect of the compression in this process at one magnitude (1.0 MPa) for 6, 12, 18, 24 and 36 h. Cell viability was measured by cell counting kit-8. Apoptosis rate was analyzed by flow cytometry and the morphologic changes in apoptosis cells were observed by the phase-contrast microscopy and Hoechst 33258 staining. The apoptosis-related gene and protein synthesis, such as Bax, Bcl-2 and Caspase-3, was analyzed by real-time polymerase chain reaction and Western-blot, respectively. Mitochondrial function was evaluated by analyzing the mitochondrial permeability transition pore (MPTP), as well as reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). The results indicated that compression at the magnitude of all time points induced apoptosis of rabbit NP cells in a time-dependent manner, and the cell viability was reduced significantly. Furthermore, the compression at this level profoundly suppressed the functions of the mitochondria such as the opening of MPTP, the excessive production of ROS and the decreased MMP. Our findings suggest that the compression-induced IVD degeneration is mediated, at least in part, via the mitochondrial apoptotic pathway in NP cells.

Arthroscopic Treatment of Calcific Tendinitis of Gemellus Superior and Gemellus Inferior: A Case Report and Literature Review.

BACKGROUND: Tendon calcification is a common disease, and it could happen in the tendons of the shoulder, wrist, etc. However, tendon calcification in the superior and inferior gemellus is rare, and in this region is likely to be misdiagnosed. CASE PRESENTATION: Here, our case report first reported a 53-year-old female patient with an unusual case of calcific tendinitis of the gemellus superior and gemellus inferior muscles. The patient presented with severe pain in the right hip and lower extremities, not relieved using nonsteroidal anti-inflammatory drugs (NSAIDs). The preoperative physical examination indicated an abnormality in the hip joint. Preoperative imaging confirmed the results of the physical examination and showed a right hip lesion. We did not make a definite diagnosis preoperatively but considered that the patient might have an osteochondroma. However, surgical findings indicated that the lesion was not in the hip capsule on subsequent arthroscopic surgery, which suggested that the preoperative diagnosis might be wrong. We opened the posterior capsule and found a "toothpaste-like" lesion in the superior and inferior gemellus muscles' tendon. We thought this might be the calcified tendon. Then the arthroscopic surgery was finished to remove the lesion, and the removed tissue was sent to the pathology department for pathological examination. The pathological report confirmed the diagnosis of the calcified tendon. Postoperative follow-up was conducted. The effect of the operation was noticeable. Postoperative symptoms were relieved. CONCLUSIONS: Calcification of the tendons of the superior and inferior gemellus muscles can be easily misdiagnosed, and the disease can be treated minimally with arthroscopy.

SP1-induced long non-coding RNA SNHG6 facilitates the carcinogenesis of chondrosarcoma through inhibiting KLF6 by recruiting EZH2.

Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma cells. Mechanistic study revealed that SNHG6 could recruit EZH2 and maintain high level of H3K27me3 to repress the transcription of tumor-suppressor genes, including KLF6. KLF6 was found to bind to the promoter region of SP1 and restrained its transcription, while SP1 could be recruited to the promoter region of SNHG6 and promoted its transcription to form a positive loop. In summary, this study reveals that SP1-induced SNHG6 forms a positive loop to facilitate the carcinogenesis of chondrosarcoma through the suppression of KLF6 by recruiting EZH2, which manifests the oncogenic function of SNHG6 in chondrosarcoma.

Recent advances of drug delivery nanocarriers in osteosarcoma treatment.

Osteosarcoma is the most common primary malignant bone tumor mainly occurred in children and adolescence, and chemotherapy is limited for the side effects and development of drug resistance. Advances in nanotechnology and knowledge of cancer biology have led to significant improvements in developing tumor-targeted drug delivery nanocarriers, and some have even entered clinically application. Delivery of chemotherapeutic agents by functionalized smart nanocarriers could protect the drugs from rapid clearance, prolong the circulating time, and increase the drug concentration at tumor sites, thus enhancing the therapeutic efficacy and reducing side effects. Various drug delivery nanocarriers have been designed and tested for osteosarcoma treatment, but most of them are still at experimental stage, and more further studies are needed before clinical application. In this present review, we briefly describe the types of commonly used nanocarriers in osteosarcoma treatment, and discuss the strategies for osteosarcoma-targeted delivery and controlled release of drugs. The application of nanoparticles in the management of metastatic osteosarcoma is also briefly discussed. The purpose of this article is to present an overview of recent progress of nanoscale drug delivery platforms in osteosarcoma, and inspire new ideas to develop more effective therapeutic options.

Application of Finite Element Analysis for Investigation of Intervertebral Disc Degeneration: from Laboratory to Clinic.

Due to the ethical concern and inability to detect inner stress distributions of intervertebral disc (IVD), traditional methods for investigation of intervertebral disc degeneration (IVDD) have significant limitations. Many researchers have demonstrated that finite element analysis (FEA) is an effective tool for the research of IVDD. However, the specific application of FEA for investigation of IVDD has not been systematically elucidated before. In the present review, we summarize the current finite element models (FEM) used for the investigation of IVDD, including the poroelastic nonlinear FEM, diffusive-reactive theory model and cell-activity coupled mechano-electrochemical theory model. We further elaborate the use of FEA for the research of IVDD pathogenesis especially for nutrition and biomechanics associated etiology, and the biological, biomechanical and clinical influences of IVDD. In addition, the application of FEA for evaluation and exploration of various treatments for IVDD is also elucidated. We conclude that FEA is an excellent technique for research of IVDD, which could be used to explore the etiology, biology and biomechanics of IVDD. In the future, FEA may help us to achieve the goal of individualized precision therapy.

Application and Prospect of Mixed Reality Technology in Medical Field.

Mixed reality (MR) technology is a new digital holographic image technology, which appears in the field of graphics after virtual reality (VR) and augmented reality (AR) technology, a new interdisciplinary frontier. As a new generation of technology, MR has attracted great attention of clinicians in recent years. The emergence of MR will bring about revolutionary changes in medical education training, medical research, medical communication, and clinical treatment. At present, MR technology has become the popular frontline information technology for medical applications. With the popularization of digital technology in the medical field, the development prospects of MR are inestimable. The purpose of this review article is to introduce the application of MR technology in the medical field and prospect its trend in the future.

Application of the Guiding Template Designed by Three-dimensional Printing Data for the Insertion of Sacroiliac Screws: a New Clinical Technique.

This study is aimed to explore the clinical application of the guiding template designed by three-dimensional printing data for the insertion of sacroiliac screws. A retrospective study of 7 cases (from July 2016 to December 2016), in which the guiding template printed by the threedimensional printing technique was used for the insertion of sacroiliac screws of patients with posterior ring injuries of pelvis, was performed. Totally, 4 males and 3 females were included in template group, aged from 38 to 65 years old (mean 50.86±8.90). Of them, 5 had sacral fractures (3 with Denis type I and 2 with type II) and 2 the separation of sacroiliac joint. Guiding templates were firstly made by the three-dimensional printing technique based on the pre-operative CT data. Surgical operations for the stabilization of pelvic ring by applying the guiding templates were carried out. A group of 8 patients with sacroiliac injuries treated by percutaneous sacroiliac screws were analyzed as a control group retrospectively. The time of each screw insertion, volume of intra-operative blood loss, and the exposure to X ray were analyzed and the Matta's radiological criteria were used to evaluate the reduction quality. The Majeed score was used to evaluate postoperative living quality. The visual analogue scale (VAS) was applied at different time points to judge pain relief of coccydynia. All the 7 patients in the template group were closely followed up radiographically and clinically for 14 to 20 months, mean (16.57±2.44) months. Totally 9 sacroiliac screws for the S1 and S2 vertebra were inserted in the 7 patients. The time length for each screw insertion ranged from 450 to 870 s, mean (690.56±135.68) s, and the number of times of exposure to X ray were 4 to 8, mean (5.78±1.20). The intra-operative blood loss ranged from 45 to 120 mL, mean (75±23.32) mL. According to Matta's radiology criteria, the fracture and dislocation reduction were excellent in 6 cases and good in 1. The pre-operative VAS score ranged from 5.2 to 8.1, mean (7.13±1.00). The average one-week/six-month post-operative VAS was (5.33±0.78) and (1.33±0.66), respectively (P<0.05 when compared with pre-operative VAS). The 12-month postoperative Majeed score ranged from 86 to 92, mean (90.29±2.21). The three-dimensional printed guiding template for sacroiliac screw insertion, which could significantly shorten the operation time, provide a satisfied outcome of the stabilization of the pelvic ring, and protect doctors and patients from X-ray exposure, might be a practical and valuable new clinical technique.

Epigenetic silencing of SFRP5 promotes the metastasis and invasion of chondrosarcoma by expression inhibition and Wnt signaling pathway activation.

BACKGROUD/AIMS: Abnormal activation of the Wnt/ß-catenin signaling, which may be antagonized by the members of secreted frizzled-related proteins family (SFRPs), is implicated in tumor occurrence and development. However, the function of SFRP5 relating to Wnt/ß-catenin pathway in chondrosarcoma is not clear yet. This study was undertaken to investigate the potential role of SFRP5 promoter methylation in chondrosarcoma metastasis and invasion through activating canonical Wnt signaling pathway. METHODS AND RESULTS: The results demonstrated that SFRP5 promoter was hypermethylated and SFRP5 expression was significantly reduced in chondrosarcoma cell lines at the mRNA and protein levels. The canonical Wnt/ß-catenin signaling was observably activated with ß-catenin stabilization by dephosphorylation and translocation into the nuclear. 5-Aza-2'-deoxycytidine (5-Aza-dC), the DNA methyltransferase inhibitor, significantly inhibited the proliferation of chondrosarcoma cells by cell cycle arrest through repressing the methylation of SFRP5 and promoting its expression. Both 5-Aza-dC treatment and SFRP5 overexpression could significantly inhibited the metastasis and invasion of chondrosarcoma cells by inactivating Wnt/ß-catenin signaling pathway and promoting chondrosarcoma cells mesenchymal-epithelial transition (MET). 5-Aza-dC also inhibited the xenograft growth and lung metastasis of chondrosarcoma cells in vivo via suppressing SFRP5 promotor methylation, inactivating Wnt/ß-catenin pathway and inducing epithelial markers expression. CONCLUSION: All of our results revealed the epigenetic silencing of SFRP5 by promoter methylation plays pivotal roles in chondrosarcoma development and metastasis through SFRP5/Wnt/ß-catenin signaling axis. Modulation of their levels may serve as potential targets and diagnostic tools for novel therapeutic strategies of chondrosarcoma.

Cooperative Assembly of a Peptide Gelator and Silk Fibroin Afford an Injectable Hydrogel for Tissue Engineering.

Silk fibroin (SF) from Bombyx mori has received increasing interest in biomedical fields, because of its slow biodegradability, good biocompatibility, and low immunogenicity. Although SF-based hydrogels have been studied intensively as a potential matrix for tissue engineering, weak gelation performance and low mechanical strength are major limitations that hamper their widespread applicability. Therefore, searching for new strategies to improve the SF gelation property is highly desirable in tissue engineering research. Herein, we report a facile approach to induce rapid gelation of SF by a small peptide gelator (e.g., NapFF). Following the simple mixing of SF and NapFF in water, a stable hydrogel of SF was obtained in a short time period at physiological pH, and the minimum gelation concentration of SF can reach as low as 0.1%. In this process of gelation, NapFF not only can behave itself as a gelator for supramolecular self-assembly, but also can trigger the conformational transition of the SF molecule from random coil to ß-sheet structure via hydrophobic and hydrogen-bonding interactions. More importantly, for the generation of a scaffold with favorable cell-surface interactions, a new peptide gelator (NapFFRGD) with Arg-Gly-Asp (RGD) domain was applied to functionalize SF hydrogel with improved bioactivity for cell adhesion and growth. Following encapsulating the vascular endothelial growth factor (VEGF), the SF gel was subcutaneously injected in mice, and served as an effective matrix to trigger the generation of new blood capillaries in vivo.

Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells.

AIMS: Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells. MATERIALS AND METHODS: Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca2+]i) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. KEY FINDINGS: Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca2+]i. In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells. SIGNIFICANCE: These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD.

TRAIL-R1 as a novel surface marker for circulating giant cell tumor of bone.

Giant cell tumor of bone (GCT), which frequently occurs in the patients' spine, is relatively prevalent in Chinese population. A group of GCT invades into vessels and appears to be circulating tumor cells (CTCs) responsible for the distal metastasis of the primary tumor. So far the cell surface markers of GCT have not been determined. In the current study, we aimed to identify a novel CTC marker with higher specificity in GCT. TRAIL-R1+ cells were purified from GCT cell lines. The TRAIL-R1+ cells were compared with total GCT cells for tumor sphere formation, chemo-resistance, tumor formation in nude mice, and frequency of developing distal metastases. We found that TRAIL-R1+ GCT cells appeared to be highly enriched for CTCs in GCT. Compared to total GCT cells, TRAIL-R1+ GCT cells generated significantly more tumor spheres in culture, were higher chemo-resistant, and had a higher frequency of being detected in the circulation after subcutaneous transplantation as well as development of distal metastases. Thus, we conclude that TRAIL-R1+ may be a novel CTC marker in GCT. Selective elimination of TRAIL-R1+ GCT cells may improve the current GCT therapy.

In vitro effect of microRNA-107 targeting Dkk-1 by regulation of Wnt/ß-catenin signaling pathway in osteosarcoma.

BACKGROUND: The aim of the study was to explore the effects of microRNA-107 (miR-107) by targeting Dkk-1 on osteosarcoma (OS) via the Wnt/ß-catenin signaling pathway. METHODS: OS and adjacent tissues were collected from 67 patients diagnosed with OS. Expressions of miR-107, Dkk-1, LRP5, ß-catenin, and c-Myc were detected by the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The dual-luciferase reporter gene assay was performed to observe the relationship between miR-107 and Dkk-1.Transfected cells were divided into different investigating groups designated as Inhibitor, Mimic, siRNA, Inhibitor + siRNA, negative control (NC), and blank groups. qRT-PCR and Western blotting were used to detect expressions of miR-107, Dkk-1, ß-catenin, Bcl-2, c-Myc, Caspase-3, and PARP. Cell counting kit-8 (CCK-8), flow cytometry (FCM), colony-formation efficiency (CFE), and subcutaneous tumorigenicity assays were all utilized for to determine cell proliferation, apoptosis, colony-forming, and tumorigenic abilities. RESULTS: Dkk-1 is the target gene of miR-107. Decreased expressions of miR-107, LRP5, ß-catenin, and c-Myc, and increased expressions of Dkk-1 were found in OS tissues. The Mimic and siRNA groups exhibited decreased proliferation rates, colony-forming abilities, and tumorigenicity and increased apoptosis rates, whereas the inhibitor group showed opposite trends when compared to the blank group. On the other hand, expressions of miR-107, LRP5, ß-catenin, c-Myc, Caspase-3, and PARP were all elevated in the mimic group, whereas expressions of Dkk-1 and Bcl-2 were reduced; opposite trends were observed in the inhibitor group. CONCLUSION: We conclude that miR-107 is likely to inhibit the occurrence and development of OS by down-regulating Dkk-1 via the Wnt/ß-catenin signaling pathway, providing us with a new therapeutic target for the treatment of OS.