Impact of dyslipidemia on the severity of symptomatic lumbar spine degeneration: A retrospective clinical study.

Background: Lumbar intervertebral disc degeneration (IVDD) is an important cause of low back pain or sciatica, and metabolic factors play an important role. However, little is known about the relationship of dyslipidemia to the risk of intervertebral disc degeneration (IVDD). This study aimed to assess the impact of serum lipid levels on the severity of lumbar disc degeneration and to investigate its association with endplate inflammation. Methods: We conducted a case retrospective study in which a total of 302 hospitalized Chinese patients were recruited, of whom 188 (112 males and 76 females; mean age: 51.66 years) were without underlying disease, while the remaining 114 patients (51 males and 63 females; mean age: 62.75 years) had underlying diseases. We examined fasting serum lipid levels for total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Magnetic resonance imaging (MRI) was used to determine endplate inflammation. Pfirrmann grading and Weishaupt grading were used to evaluate the severity of intervertebral disc degeneration and facet joint degeneration, respectively. Results: There was no difference in age, gender, and general BMI between the two groups (P > 0.05), but there were significantly high levels in TC, LDL-C, and LDL-C/HDL-C (P = 0.04, P = 0.013, P = 0.01, respectively). TG and HDL-C showed no significant difference (P = 0.064, P = 0.336, respectively). The multivariate logistic regression model showed that age was a risk factor for the occurrence of endplate inflammation. In the group without underlying diseases, age, but not other indicators, was a risk factor for the occurrence of endplate inflammation (P < 0.01), In the group with underlying diseases, none of the patient indicators was directly related to the occurrence of endplate inflammation (P > 0.05). A nonlinear machine learning model was used to measure the contribution of each factor to the disease outcome and to analyze the effect between the top three contributing factors and the outcome variables. In patients without underlying diseases, the top three factors contributing to the severity grading of intervertebral disc degeneration were age (32.9%), high-density lipoproteins (20.7%), and triglycerides (11.8%). For the severity grading of facet joint degeneration, the top three contributing factors were age (27.7%), high-density lipoproteins (19.4%), and triglycerides (14.6%). For patients with underlying diseases, the top three factors contributing to intervertebral disc degeneration were age (25.4%), BMI (15.3%), and low-density lipoprotein/high-density lipoprotein ratio (13.9%). In terms of degree classification for facet joint degeneration, the top three contributing factors were age (17.5%), BMI (17.2%), and total cholesterol (16.7%). Conclusion: This study shows that age, high-density lipoprotein, and triglycerides affect the degree of degeneration in patients with symptomatic lumbar degeneration without underlying diseases. Age and BMI are two major factors affecting the severity of degeneration in patients with underlying diseases, and dyslipidemia is a secondary factor. However, there is no clear association between dyslipidemia and the occurrence of endplate inflammation in either group.

Dream-Experiment: A MR User Interface with Natural Multi-channel Interaction for Virtual Experiments.

This paper studies a set of MR technologies for middle school experimental teaching environments and develops a multi-channel MR user interface called Dream-Experiment. The goal of Dream-Experiment is to improve the traditional MR user interface, so that users can get a real, natural 3D interactive experience like real experiments, but without danger and pollution. In terms of visual presentation, we design multi-camera collaborative registration to realize robust 6-DoF MR interactive space, and also define a complete rendering pipeline to provide improved processing of virtual-real objects' occlusion including translucent devices. In the virtual-real interaction, we provide six interaction modes that support visual interaction, tangible interaction, virtual-real gestures with touching, voice, thermal feeling, and olfactory feeling. After users' testing, we find that Dream-Experiment has better interactive efficiency and user experience than traditional MR environments.

Photoacoustic stimulation promotes the osteogenic differentiation of bone mesenchymal stem cells to enhance the repair of bone defect.

The aim of this study was to evaluate the direct photoacoustic (PA) effect on bone marrow mesenchymal stem cells (BMSCs) which is a key cell source for osteogenesis. As scaffold is also an indispensable element for tissue regeneration, here we firstly fabricated a composited sheet using polylactic-co-glycolic acid (PLGA) mixing with graphene oxide (GO). BMSCs were seeded on the PLGA-GO sheets and received PA treatment in vitro for 3, 9 and 15 days, respectively. Then the BMSCs were harvested and subjected to assess alkaline phosphatase (ALP) activity, calcium content and osteopontin (OPN) on 3, 9 and 15 days. For in vivo study, PLGA-GO sheet seeded with BMSCs after in vitro PA stimulation for 9 days were implanted to repair the bone defect established in the femoral mid-shaft of Sprague-Dawley rat. PLGA-GO group with PA pretreatment showed promising outcomes in terms of the expression of ALP, OPN, and calcium content, thus enhanced the repair of bone defect. In conclusion, we have developed an alternative approach to enhance the repair of bone defect by making good use of the beneficial effect of PA.

MiR-19a regulates the cell growth and apoptosis of osteosarcoma stem cells by targeting PTEN.

MicroRNAs are small, endogenous, and non-coding RNAs that play important regulatory roles in multiple biological processes in cancers. Recent evidence has indicated that miR-19a participates in the cancer tumorigenic progression. However, the functional roles of miR-19a in cancer stem cells are still unclear. As the cancer stem cells are considered to be responsible for the tumor recurrence and treatment failure in osteosarcoma, the aim of this study is to investigate the molecular mechanism of miR-19a underlying osteosarcoma tumorigenesis. In this study, we observed significant upregulation of miR-19a in osteosarcoma patients' tumor tissues as well as the osteosarcoma cell lines in vitro. We showed that knockdown of miR-19a by its antisense oligonucleotide (anti-miR-19a) significantly decreased the population of cancer stem cells in osteosarcoma cell lines. Furthermore, we found the miR-19a regulated the cell proliferation, migration, and viability in the human osteosarcoma-cancer stem cells. The gene of phosphatase and tensin homolog deleted on chromosome 10, which is an important tumor suppressor, was found to be directly regulated by miR-19a in human osteosarcoma-cancer stem cells. We demonstrated that knockdown of miR-19a increased the expression of phosphatase and tensin homolog deleted on chromosome 10. As the anti-miR-19a inhibited the phosphatidylinositol 3-kinase/AKT pathway and induced apoptosis of human osteosarcoma-cancer stem cells, the phosphatase and tensin homolog deleted on chromosome 10 small interfering RNA inhibited the effect of it. Meanwhile, the phosphatase and tensin homolog deleted on chromosome 10 small interfering RNA also abolished the effect of anti-miR-19a on inhibiting the cell proliferation, migration, and viability in the human osteosarcoma-cancer stem cells. In conclusion, our findings demonstrated that dysregulation of miR-19a plays critical roles in the osteosarcoma stem cells, at least in part via targeting the phosphatase and tensin homolog deleted on chromosome 10. Knockdown of miR-19a may represent a potential strategy for the osteosarcoma treatment.

An Innovative Approach for Enhancing Bone Defect Healing Using PLGA Scaffolds Seeded with Extracorporeal-shock-wave-treated Bone Marrow Mesenchymal Stem Cells (BMSCs).

Although great efforts are being made using growth factors and gene therapy, the repair of bone defects remains a major challenge in modern medicine that has resulted in an increased burden on both healthcare and the economy. Emerging tissue engineering techniques that use of combination of biodegradable poly-lactic-co-glycolic acid (PLGA) and mesenchymal stem cells have shed light on improving bone defect healing; however, additional growth factors are also required with these methods. Therefore, the development of novel and cost-effective approaches is of great importance. Our in vitro results demonstrated that ESW treatment (10 kV, 500 pulses) has a stimulatory effect on the proliferation and osteogenic differentiation of bone marrow-derived MSCs (BMSCs). Histological and micro-CT results showed that PLGA scaffolds seeded with ESW-treated BMSCs produced more bone-like tissue with commitment to the osteogenic lineage when subcutaneously implanted in vivo, as compared to control group. Significantly greater bone formation with a faster mineral apposition rate inside the defect site was observed in the ESW group compared to control group. Biomechanical parameters, including ultimate load and stress at failure, improved over time and were superior to those of the control group. Taken together, this innovative approach shows significant potential in bone tissue regeneration.

Prostaglandin E2 and Connexin 43 crosstalk in the osteogenesis induced by extracorporeal shockwave.

As a type of mechanical stimulation, extracorporeal shockwave (ESW) has been widely used in the clinic to treat bone fracture delayed union and non-unions. A large number of studies have shown beneficial effects of ESW in promoting fracture healing by inducing bone regeneration; however, the underlying mechanisms remain unclear. ESW has been shown to induce the production of prostaglandin E2 (PGE2), which is essential for gap junction intercellular communication in response to mechanical stress. Among the 19 known gap junction subunits, connexin43 (Cx43) is the most prevalent for mediating the response of mechanical stress. However, to our knowledge, the effect of ESW on Cx43 expression has not been reported before. Herein, we propose that a crosstalk between PGE2 and Cx43 is involved in the enhancement of osteogenesis induced by ESW. We review the currently available data to propose an unrevealed, but important mechanism via which ESW treatment affects osteogenic differentiation of bone marrow stromal cells.

Focal Adhesion Kinase Signaling Mediated the Enhancement of Osteogenesis of Human Mesenchymal Stem Cells Induced by Extracorporeal Shockwave.

Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs) and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate the underlying mechanisms. We show here that ESW (0.16 mj/mm(2)) significantly promoted the osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of miR-138, but the activation of FAK, ERK1/2, and RUNX2. The enhancement of osteogenesis in these MSCs was consistently abolished when the cells were pretreated with one of the following conditions: overexpression of miR-138, FAK knockdown using specific siRNA, and U0126, implying that all of these elements are indispensable for mediating the effect of ESW. Moreover, our study provides converging genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally activated in ESW-preconditioned MSCs, suggesting that ESW may be a promising therapeutic strategy for the enhancement of osteogenesis of MSCs, regardless of their origins.

MicroRNA-145 Suppresses Osteosarcoma Metastasis via Targeting MMP16.

BACKGROUND: Metastasis is a leading cause of mortality for osteosarcoma (OS) patients, and its molecular pathological mechanisms remain to be elucidated. Previous studies have suggested a significant role of microRNAs (miRNAs) in the control of cancel cell migration and invasion. METHODS: Real-time PCR was used to screen the differentially expressed miRNAs between OS with or without metastasis, and miR-145 underexpression was observed in metastatic OS. Luciferase assay was performed to validate the target gene. RESULTS: Further, we identified three genes, MMP16, ADAM17 and metadherin, as possible targets of miR-145. We identified MMP16 as a target gene of miR-145 and ruled out ADAM17 and metadherin as targets in OS using a dual luciferase reporter system. Subsequently, we determined and compared the expression level of MMP16 in human OS samples and showed that the mRNA and protein levels of MMP16 were significantly up-regulated in primary OS with metastasis compared with those without metastasis. We also altered miR-145 expression by transfecting OS cells with miR-145 mimics or inhibitors. MMP16 expression was similarly downregulated in the cells transfected with miR-145 mimics or MMP16-specific siRNA, and the invasive and migratory capability of those cells was significantly suppressed compared with negative controls. MMP16 expression was consistently significantly upregulated in the cells transfected with miR-145 inhibitors, and the invasive and migratory capability of those cells was significantly promoted compared with negative controls. Conclcusion: Our results suggest that miR-145 functions as a tumor metastasis suppressor gene by down-regulating MMP16 and may be a potential target in osteosarcoma treatment.