Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering.

Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.

Advances in materials used for minimally invasive treatment of vertebral compression fractures.

Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and summarize the approaches for improving the characteristics of bone cement. Finally, we review the types and clinical efficacy of new vertebral implants. This review may provide valuable insights into newer strategies and methods for future research; it may also improve understanding on the application of minimally invasive materials for the treatment of vertebral compression fractures.

The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.

Osteosarcoma (OS) is one of the most aggressive bone tumors worldwide. Emerging documents have shown that long noncoding RNAs (lncRNAs) elicit crucial regulatory functions in the process of tumorigenesis. LncRNA DLGAP1-AS2 is recognized as a regulator in several types of cancers, but its biological functions and molecular mechanisms in OS remain to be elucidated. RT-qPCR and In situ hybridization (ISH) were used to evaluate DLGAP1-AS2 expression in OS samples. Western blotting was used for the measurement of the protein levels of hexokinase 2 (HK2) and epithelial-mesenchymal transition (EMT)-related markers. The proliferation of OS cells was determined using a CCK-8 assay and EdU assay. TUNEL assay and flow cytometry were performed to assess OS cell apoptosis. Glucose metabolism in vitro assays were used. The binding relations among miR-451a, HK2, and DLGAP1-AS2 were validated by luciferase reporter assay. The cellular distribution of DLGAP1-AS2 in OS cells was determined by FISH and subcellular fractionation assays. Mouse xenograft models were established to perform the experiments in vivo. We found that DLGAP1-AS2 expression was upregulated in OS tissues and cells. Downregulation of DLGAP1-AS2 expression suppressed the malignancy of OS cells by restraining cell proliferation, the EMT process, invasiveness, migration, and aerobic glycolysis and accelerating apoptotic behaviors. Of note, silenced DLGAP1-AS2 restrained tumor growth and metastasis in vivo. However, DLGAP1-AS2 overexpression accelerated the progression of OS. We further found that DLGAP1-AS2 upregulation was induced by hypoxia and low glucose. Additionally, DLGAP1-AS2 bound to miR-451a to upregulate HK2 expression. Rescue assays revealed that the DLGAP1-AS2/miR-451a/HK2 axis contributed to OS cell malignancy by promoting aerobic glucose metabolism. Overall, these findings revealed a new regulatory pathway where DLGAP1-AS2 upregulated HK2 expression by sponging miR-451a to accelerate OS development.

Circ_0001825 promotes osteogenic differentiation in human-derived mesenchymal stem cells via miR-1270/SMAD5 axis.

BACKGROUND: The implication of deregulated circular RNAs in osteoporosis (OP) has gradually been proposed. Herein, we aimed to study the function and mechanism of circ_0001825 in OP using osteogenic-induced human-derived mesenchymal stem cells (hMSCs). METHODS: The content of genes and proteins was tested by quantitative real-time polymerase chain reaction and Western blotting. The osteogenic differentiation in hMSCs were evaluated by ALP activity and Alizarin Red staining, as well as the detection of osteogenesis-related markers. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry. The binding between miR-1270 and circ_0001825 or SMAD5 (SMAD Family Member 5) was confirmed by using dual-luciferase reporter assay and pull-down assay. RESULTS: Circ_0001825 was lowly expressed in OP patients and osteogenic induced hMSCs. Knockdown of circ_0001825 suppressed hMSC viability and osteogenic differentiation, while circ_0001825 overexpression showed the exact opposite effects. Mechanistically, circ_0001825/miR-1270/SMAD5 formed a feedback loop. MiR-1270 was increased and SMAD5 was decreased in OP patients and osteogenic induced hMSCs. MiR-1270 up-regulation suppressed hMSC viability and osteogenic differentiation, which was reversed by SMAD5 overexpression. Moreover, miR-1270 deficiency abolished the effects of circ_0001825 knockdown on hMSCs. CONCLUSION: Circ_0001825 promoted hMSC viability and osteogenic differentiation via miR-1270/SMAD5 axis, suggesting the potential involvement of circ_0001825 in osteoporosis.

Causality and interdependencies among sustainable development goals: assessing the nexus of agriculture, environment, and finance development.

This study examines the causal relationships and interdependencies among three dimensions of sustainable development goals (SDGs) in Africa: environmental factors, agricultural production (for societal aspects), and finance development (for economic aspects). The study focuses on three regions, the whole SSA (Sub-Saharan Africa, excluding the high-income countries), West-Central Africa (W-CA), and South and East Africa (S-EA), and uses data from 1970 to 2018. It uses vector error correction model (VECM), impulse response function (IRF), and analysis of causality direction methods. The findings indicate bidirectional causal effects among the three SDG dimensions in Africa. Finance development factors influence both environmental and agricultural factors, while agro-production factors significantly affect both finance development and environmental factors. This study concludes that bidirectional causal effects exist within these dimensions, confirming their interdependencies and emphasizing the need for integrating these dimensions into African sustainable development goals. Recommendations include incorporating green aspects in financing development plans and establishing regulatory authorities to effectively coordinate and control these sustainable dimensions at both the Sub-Saharan Africa and state levels, ensuring impactful greenhouse and sustainable agriculture development for sustainable food production.

A free field recovery technique based on the boundary element method and three-dimensional scanning measurements.

The boundary element method- (BEM-) based free field recovery technique (FFRT) has been proposed to recover the free field radiated by an arbitrarily shaped source from the mixed field that would be measured in a noisy environment. However, that technique requires that the boundary integral equation should be established on an enclosed hologram surface surrounding the source, which means that the hologram surface should be discretized into elements and the measurement points should be located on the nodes of the elements. For large-scale or mid-high frequency problems, it makes the total number of measurement points huge since it should obey the criterion of more than six elements per wavelength, which put forward very high requirements for holographic data measurement. To overcome this problem, a more flexible BEM-based FFRT without the restriction on the locations of measurement points is proposed in this study. In virtue of this, a three-dimensional scanning measurement method can be applied to acquire holographic data with high efficiency. The effectiveness of the proposed method is validated by two numerical simulations and an experiment.

Role and Mechanism of circ_0058063/miR-635 Axis in the Malignant Phenotype of Multiple Myeloma RPMI8226 Cells.

OBJECTIVE: This study aims to explore circ_0058063 effect on multiple myeloma cells malignant phenotype and its feasible mechanism. METHODS: We selected 47 cases of multiple myeloma tissues and 47 cases of normal bone marrow tissues and then used RT-qPCR method to test circ_0058063 and miR-635 expression in the tissues. Myeloma cells RPMI8226 were transfected with si-circ_0058063, miR-635 mimic, and si-circ_0058063 + anti-miR-635, respectively. Then, we adopt CCK-8 method, flow cytometry method, and Transwell and western blot methods to detect the influences of knockdown of circ_0058063 or miR-635 overexpression on RPMI8226 cell proliferation, apoptosis, migration, and invasion and also Ki-67, Bax, Bcl-2, MMP-2, and MMP-9 protein expression. The dual luciferase reporter gene assay experiment proved that it has regulatory relationship between circ_0058063 and miR-635. RESULTS: circ_0058063 expression of multiple myeloma was higher than that in normal bone marrow tissue (P < 0.05), while miR-635 expression was lower than that in normal bone marrow tissue (P < 0.05). Knockdown of circ_0058063 or overexpression of miR-635 could reduce proliferation capacity, migration, invasion cell quantities, and Ki-67, MMP-2, MMP-9, and Bcl-2 protein expression (P < 0.05), while increasing apoptosis rate together with Bax protein expression (P < 0.05). circ_0058063 targets to negatively regulate miR-635, while knocking down miR-635 reverses the influences of knocking down circ_0058063 on RPMI8226 proliferation, apoptosis, migration, and invasion. CONCLUSION: circ_0058063 expression increased in multiple myeloma tissues. Knocking down its expression may inhibit myeloma proliferation, migration, and invasion by targeting and upregulating miR-635 and also promote cell apoptosis. As for multiple myeloma treatment, circ_0058063/miR-635 may provide new molecular targets.

LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-ß/SMAD Signaling Pathway and Upregulating SSH2 Expression.

Osteosarcoma (OS), a frequent malignant tumor which mainly occurs in the bone. The roles of long noncoding RNAs (lncRNAs) have been revealed in cancers, including OS. LncRNA long intergenic non-protein coding RNA (LINC00174) has been validated as an oncogene in several cancers. However, the role of LINC00174 in OS has not been explored. In our research, loss-of-function assays were conducted to explore the function of LINC00174 in OS cells. Then, we explored the downstream pathway of LINC00174 in OS cells. Bioinformatics, RNA pull-down and RIP experiments investigated the downstream mechanism of LINC00174 in OS cells. Finally, in vivo assays clarified the effect of LINC00174 on tumorigenesis. We found that LINC00174 was upregulated in OS tissues and cells. LINC00174 knockdown repressed OS cell growth. Mechanistically, LINC00174 knockdown suppressed the TGF-ß/SMAD pathway. LINC00174 interacted with miR-378a-3p, and slingshot protein phosphatase 2 (SSH2) 3'UTR was targeted by miR-378a-3p in OS cells. Rescue assays showed that SSH2 upregulation or miR-378a-3p inhibition counteracted the inhibitory effect of LINC00174 depletion in OS cell growth. Additionally, LINC00174 depletion suppressed tumor growth in mice. In conclusion, LINC00174 promotes OS cellular malignancy and tumorigenesis via the miR-378a-3p/SSH2 axis and the TGF-ß/SMAD pathway, which might provide a novel insight for OS treatment.

Aberrantly DNA Methylated-Differentially Expressed Genes in Pancreatic Cancer Through an Integrated Bioinformatics Approach.

Pancreatic cancer remains one of the chief contributors to cancer related deaths on a global scale, with its diagnosis often associated with poor prognosis and high mortality. Accumulating literature continues to highlight the role of aberrant DNA methylation in relation to pancreatic cancer progression. Integrated bioinformatics approaches in the characterization of methylated-differentially expressed genes (MeDEGs) in pancreatic cancer were employed to enhance our understanding of the potential underlying molecular mechanisms of this cancer. We initially identified differentially expressed genes (DEGs) between 178 pancreatic cancer samples and 4 normal samples and differentially methylated genes (DMGs) based on 185 pancreatic cancer samples as well as 10 normal samples by analyzing RNA sequencing data in the TCGA database. Eventually, 31 MeDEGs including 5 hypomethylated/upregulated genes and 26 hypermethylated/downregulated genes were identified. Univariate Cox model and Kaplan-Meier method revealed that, among 31 MeDEGs, 5 hypermethylated/downregulated genes (ZNF804A, ZFP82, TRIM58, SOX17, and C12orf42) were correlated with poor survival of patients with pancreatic cancer. KEGG pathway enrichment analysis by GSEA 3.0 and the protein-protein interaction (PPI) network revealed that these 5 MeDEGs were enriched in numerous cancer-related pathways in addition to interacting with each other, highlighting a significant role in the development of pancreatic cancer. Taken together, the key findings of the current study demonstrate that ZNF804A, ZFP82, TRIM58, SOX17, and C12orf42 are hypermethylated/downregulated genes in pancreatic cancer and may be associated, through their modulation of specific pathways, with unfavorable pancreatic cancer prognosis.

Sensitivity analysis of acoustic eigenfrequencies by using a boundary element method.

This paper presents a boundary element-based scheme for the sensitivity analysis of acoustic eigenfrequencies of both interior and exterior acoustic systems. The nonlinear eigenvalue problem generated by the acoustic boundary element method is first reformulated into a generalized eigenvalue problem of reduced dimension through a contour integral approach. The sensitivity formulations for acoustic eigenfrequencies are then derived based on an adjoint method that uses both the right and left eigenvectors. The adaptive cross approximation in conjunction with the hierarchical matrices is used to reduce the solution burden of the boundary element systems. The Burton-Miller-type combined formulation is applied to shift the spurious eigenfrequencies and their sensitivities, and the strategies to identify the spurious results are suggested. Three numerical examples are used to verify the accuracy and applicability of the developed scheme.

Is there an association between peptic ulcer disease and osteoporosis: a systematic review and cumulative analysis.

BACKGROUND: Mounting studies have emerged indicating that patients with peptic ulcer disease (PUD) are at a high risk of developing osteoporosis, but the evidence has not been previously synthesized. The present study aims to examine whether patients with PUD have a significantly higher prevalence of osteoporosis than the healthy normal subjects. METHODS: Four electronic databases were systematically searched for eligible studies up to February 2020. The association between PUD and osteoporosis was evaluated by calculating the relative risk (RR) with a 95% confidence interval (CI). RESULTS: Six observational studies were finally included, enrolling a total of 216 122 individuals. Synthetic results from the six included studies providing the number of cases for both sexes demonstrated that PUD was significantly associated with an increased risk of osteoporosis (95% CI, 1.37-1.89; P < 0.001). In line with this finding, the combined effect from the three studies independently reporting the male subjects also yielded to a positive relationship between PUD and osteoporosis (RR = 2.08; 95% CI,1.10-3.93; P = 0.023). However, when restricted to female participants, pooled results indicated that women patients with PUD would not suffer significantly more risk of osteoporosis than the general women population (RR = 1.36; 95% CI, 0.84-2.21, P = 0.212). CONCLUSIONS: This is the first study for quantifying the positive association between PUD and the risk of osteoporosis by conducting a meta-analysis. In clinical practice, assessment of the bone mineral density and antiosteoporosis treatments are recommended for those potential patients with PUD.

Cloacal malformation: A rare case report and review of prenatal imagings.

RATIONALE: Cloacal malformation (CM) is a serious type of anorectal and urogenital tract malformation. However, prenatal ultrasound (US) detection of CM is challenging. In this paper, we reported a rare case of CM prenatally diagnosed by US and magnetic resonance imaging (MRI), as well as reviewed the prenatal US and MRI characteristics of CM in the literature. PATIENT CONCERNS: A 30-year-old pregnant woman complained of cystic mass in the fetal abdomen detected by prenatal US. DIAGNOSIS: Fetus CM. INTERVENTIONS: The fetus was diagnosed as fetal CM by US and MRI, then the pregnant woman received a drug-induced labor treatment. After the neonate was delivered, the measurement was performed on the weight, length, head circumference, abdomen circumference, and bilateral thigh circumference. OUTCOMES: A female dead neonate was delivered from the vagina of the gravida, showing congenital anus absence. Prenatal ultrasound demonstrated right kidney duplication, hydronephrosis, and right ureteral dilatation. Meanwhile, prenatal MRI showed a cystic cavity, double collecting systems of right kidney, right ureteral dilatation, and right rectum dilatation. In addition, general parameters are as follows: weight: 2280 g; length: 39 cm; head circumference: 26.3 cm; abdomen circumference: 31 cm; right thigh circumference: 17 cm, and left thigh circumference: 18 cm. LESSONS: US combined with MRI can not only provide reliable evidence for fetal CM in the third trimester but also offer crucial information to the pregnant women to establish clinic treatment programs as early as possible.

Estimating the acoustical properties of locally reactive finite materials using the boundary element method.

The finite size of a sound-absorbing material may lead to inaccurate results when measuring the acoustical properties of the material using the free-field measurement methods. In this study, a method of estimating the acoustical properties of locally reactive finite materials is proposed by combining a sound field model established by the boundary element method with an iteration algorithm. The proposed method takes the finiteness of the material into account, meaning that the size effect is removed and accurate results can be obtained. Numerical simulations and experiments of two kinds of materials, including a rigid floor and a porous material, are carried out to verify the validity of the proposed method. Results demonstrate that the proposed method is effective in estimating the acoustical properties of these two kinds of materials. Besides, a detailed analysis of the influences of the sample size, the source location, and the receiving point position is done in the simulations.

A boundary element eigensolver for acoustic resonances in cavities with impedance boundary conditions.

This letter presents a boundary element scheme for analysis of acoustic resonances in cavities with impedance boundary conditions. The resultant eigenproblem, which is nonlinear and difficult to solve directly, is transformed to a linear one through a contour integral method. A variant-parameter scheme based on the Burton-Miller combined formulation is given to identify spurious eigenfrequencies, which are complex and similar to true eigenfrequencies. A numerical example is used to show the accuracy and effectiveness of the proposed method.

Is There an Association Between Schizophrenia and Sexual Dysfunction in Both Sexes? A Systematic Review and Meta-Analysis.

BACKGROUND: Mounting clinical studies have reported patients with schizophrenia are at high risk of developing sexual dysfunction (SD), but a directly calculated prevalence of SD is currently lacking. AIM: To further quantify the association between schizophrenia and SD. METHODS: MEDLINE (PubMed), Embase (OVID), the Cochrane Library databases, and the PsycINFO were systematically searched for eligible studies reporting the sexual functioning in patients with schizophrenia. This meta-analysis has been registered on PROSPERO (ID: CRD42019121720, http://www.crd.york.ac.uk/PROSPERO). OUTCOMES: The relationship between schizophrenia and SD was detected by calculating the relative risk (RR) with a 95% confidence interval (CI). The GRADE-profiler was employed to rank the quality of the evidence. RESULTS: 10 observational studies (3 case-control studies and 7 cross-sectional studies) were finally included, enrolling a total of 3,570 participants (mean age 28.6-46.2 years), of whom 1,161 had schizophrenia and the remainders were the healthy control subjects. Synthetic results indicated that schizophrenia was significantly associated with an increased risk of SD regardless of gender (3 studies reporting both sexes: RR = 2.24, 95%CI: 1.66-3.03, P < .001, heterogeneity: I2 = 0.0%, P = .431; 7 studies reporting men: RR = 2.63, 95%CI: 1.68-4.13, P < .001, heterogeneity: I2 = 82.7%, P < .001; 5 studies reporting women: RR = 2.07, 95%CI: 1.46-2.94, P < .001; heterogeneity: I2 = 79.7%, P = .001). In accordance with the GRADE-profiler, the quality of the evidence of primary outcomes was LOW, MODERATE, and LOW in studies including both sexes, men, and women, respectively. CLINICAL IMPLICATIONS: Our findings confirmed the potential link between schizophrenia and SD. Clinicians should routinely assess the sexual functioning for those patients with schizophrenia and further recommend the preferred antipsychotics for them. STRENGTHS & LIMITATIONS: This is the first meta-analysis investigating the association between schizophrenia and the risks of SD in both sexes. Nonetheless, substantial heterogeneities were identified across the selected studies. CONCLUSION: Robust data from this meta-analysis showed increased rates of SD in patients with schizophrenia compared with the general populations. Therefore, more specific psychological and pharmaceutical interventions are needed to help patients with schizophrenia gain a better sexual life. Zhao S, Wang X, Qiang X, et al. Is There an Association Between Schizophrenia and Sexual Dysfunction in Both Sexes? A Systematic Review and Meta-Analysis. J Sex Med 2020;17:1476-1488.

Percutaneous vertebroplasty with granulated allogeneic bone grafting using screw-view model of navigation for thoracolumbar compressive fracture: A case report.

RATIONALE: The aim of this study was to assess the accuracy of percutaneous puncture needle with screw view model of navigation (SVMN) and the effect of periacetabular vertebroplasty (PVP) with granulated allogeneic bone grafting in thoracolumbar compressive fracture (TCF). PATIENT CONCERNS: A 46-year-old female patient associated with high fall injury showed symptoms characterized by back pain and restricted movement of the right lower extremity. DIAGNOSES: The patient was diagnosed with a TCF, right femoral neck fracture, and lumbar vertebrae hyperosteogeny. INTERVENTIONS: A SVMN was used to guide our puncture needle insertion; and PVP was performed with granulated allogeneic bone grafting in this patient. OUTCOMES: The follow-up lasted for 29 months. It took 2.4 minutes to design the trajectory of puncture needle, 2.1 minutes to implant the puncture needle, and 6.3 minutes to undergone fluoroscopy. Postoperative visual analog scale and Oswestry disability index scores were improved obviously compared with those before the operation. The Cobb angle of fractured vertebrae improved from 9.3° to 7.3° after treatment. The height ratio of fractured vertebrae increased from 79.5% to 90.6% postoperatively. Intraoperative blood loss amounted to 11 ml. No clinical complications were observed, including neurovascular injury and new fracture of adjacent vertebra. LESSONS: Puncture needle placement under the guidance of SVMN is verified as a convenient, safe and reliable method, and PVP with granulated allogeneic bone grafting can effectively restore the height of anterior fractured vertebra, filling the gaps in the fractured vertebrae, and reconstructing the completeness of the fractured vertebrae.

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury.

A novel type of programmed necrosis called necroptosis has been identified in the field of cell death, thereby offering an opportunity for re-examining necrosis after spinal cord injury (SCI). Several recent studies have suggested receptor-interacting protein kinase 3 (RIP3) plays an important role in necrosis in many cell types. However, it is still unclear what downstream events that lead to cell death are triggered by RIP3 activation. Hence, link between RIP3 inhibition and induction of neuronal cell death via mitochondrial function and antioxidative capacity after SCI was studied in our work. We examined the protective effects of RIP3 inhibition in SCI-mice. Furthermore, mimicking the pathological conditions of SCI in vitro, spinal cord neurons were subjected to oxygen-glucose deprivation. Notably, we found GSK872 and Nec-1 ameliorated the locomotor function and spinal cord edema, and conferred reverse of SCI-induced loss of mitochondrial integrity, ATP, glutathione and superoxide dismutase and elevation of reactive oxygen species and malonyldialdehyde in SCI-mice. Moreover, GSK872 alleviated OGD-inducted mitochondrial dysfunction, decreased antioxidative capacity and cell death in spinal cord neurons, through inhibiting RIP3 activity. The data suggest improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention.

miRNA-101 promotes chondrogenic differentiation in rat bone marrow mesenchymal stem cells.

Effect and related mechanisms of miR-101 on the chondrogenic differentiation of rat bone marrow mesenchymal stem cells (MSCs) were investigated. The expression level of miR-101 was detected during chondrogenic differentiation. Three groups were established to study the potential function between miR-101 and chondrogenic differentiation: miR-NC group (negative control), miR-101 mimics (BMSCs transfected by miR-101 mimics) and mimics + inhibitor (BMSCs transfected by miR-101 mimics and inhibitor), after the induction of chondrogenic differentiation, the cell viability of MSCs and chondrogenic markers were determined, further, the expression level of Sox9 and Runx2 were detected. In our present research, miR-101 was found upregulated during chondrogenic differentiation of MSCs. Compared with the miR-NC group, the cell viability of MSCs was enhanced and the expression level of chondrogenic markers were respectively gained. The expression level of Sox9 was increased but the expression level of Runx2 was decreased by treatment of miR-101 mimics after induction of chondrogenic differentiation. However, these variations of the indicators were reversed by the intervention using the miR-101 inhibitor. Collectively, our research revealed promotion function of miR-101 on chondrogenic differentiation of MSCs, indicating that miR-101 could be a potential therapeutic strategy for the treatment of osteoarthritis (OA).

MicroRNA-1270 is associated with poor prognosis and its inhibition yielded anticancer mechanisms in human osteosarcoma.

In this work, we explored the aberrant expression pattern, clinical association, and functional regulations of microRNA-1270 (miR-1270) in osteosarcoma. Among in vitro osteosarcoma cell lines and in situ tissues of osteosarcoma patients, quantitative real time-PCR was used to examine their endogenous miR-1270 expression. Clinical correlation between endogenous miR-1270 expression and clinicopathological features of osteosarcoma patients, as well as cancer patients' overall survival, was statistically examined. MiR-1270 was downregulated in 143B and MG-63 cells by lentiviral transduction. The mechanistic effects of miR-1270 downregulation on osteosarcoma in vitro proliferation and migration, as well as in vivo tumorigenesis, were further examined. MiR-1270 was aberrantly upregulated in both in vitro osteosarcoma cell lines and in situ human tumors. Statistical analysis demonstrated endogenous miR-1270 was associated with poor clinical outcomes and shorter overall survival of osteosarcoma patients. Lentivirus-induced miR-1270 downregulation inhibited cancer in vitro proliferation and migration, as well as in vivo tumorigenesis. Aberrant upregulation miR-1270 may be a prognostic biomarker for osteosarcoma patients with poor clinical outcomes and shorter survival. Inhibition of miR-1270 may also be a potential therapeutic target for anticancer treatment in osteosarcoma. © 2018 IUBMB Life, 70(7):625-632, 2018.

JTC-801 exerts anti-proliferative effects in human osteosarcoma cells by inducing apoptosis.

BACKGROUND: The research of G protein-coupled receptors (GPCRs) is a promising strategy for drug discovery. In cancer therapy, there is a need to discover novel agents that can inhibit proliferation and induce apoptosis in cancer cells. JTC-801 is a novel GPCR antagonist with the function of reversing pain and anxiety symptoms. This study aims to investigate the antitumor effects of JTC-801 on human osteosarcoma cells (U2OS) and elucidate the underlying mechanism. MATERIALS AND METHODS: The Cell Counting Kit-8 assay was used to detect the viability of U2OS cells treated with JTC-801 in vitro. The cell apoptosis was evaluated using a flow cytometry assay with Annexin V-FITC/PI double staining. The inhibitory effect of JTC-801 on invasion and migration of U2OS cells were determined by the Transwell assays. Western blot assay was performed to measure the levels of proteins related to cell apoptosis and its mechanism. RESULTS: The JTC-801 significantly decreased the viability of U2OS cells (p < .05) as a result of its anti-proliferative effect through induction of apoptosis associated with activation of BAX, Caspase-3 and down-regulating BCL-2 expression. The invasive and migratory cells were obviously reduced after JTC-801 treatment (p < .05). Further, the phosphorylated AKT, mTOR and active p70 S6 protein kinase in the PI3K/AKT signaling pathway were obviously lessened in the JTC-801 treated U2OS group (p < .05). CONCLUSIONS: JTC-801 may exert osteosarcoma cell growth inhibition by promoting cell apoptosis, through PI3K/AKT signaling pathway participation.