Alpha-lipoic Acid Prevents Bone Loss in Type 2 Diabetes and Postmenopausal Osteoporosis Coexisting Conditions by Modulating the YAP/Glut4 Pathway.

This study aims to characterize the bone-protecting effects of Alpha-lipoic acid (ALA), a potent antioxidant, against the detrimental effects of the coexistence of type 2 diabetes mellitus (T2DM) and postmenopausal osteoporosis (POP) and identify the possible mechanisms with particular reference to its modulation of YAP/Glut4 pathway. The T2DM and POP coexisting model was induced in mice by high fat diet (HFD) + Streptozocin (STZ) + ovariectomy (OVX). The mice in the treatment groups were given ALA for 10 weeks. In the in vitro study, MC3T3-E1 cells were induced with 500 µM methylglyoxal for 24 h with or without pretreatment with ALA for 24 h. The oxidative and antioxidative biomarkers, bone microarchitecture, histo-morphology, and related protein expression of apoptosis, osteogenic differentiation and the YAP/Glut4 pathway were detected. The results showed ALA could improve glucose tolerance, inhibit oxidative stress and apoptosis and alleviate bone loss. Further study by siRNA technology revealed that the YAP/Glut4 pathway was implicated in the pathogenesis of bone loss due to the coexistence of T2DM and POP. Taken together, the present study has demonstrated for the first time that ALA exerts potent protective effects against bone loss in T2DM and POP coexisting conditions by modulating the YAP/Glut4 pathway.

Coenzyme Q10 Protects Against Hyperlipidemia-Induced Osteoporosis by Improving Mitochondrial Function via Modulating miR-130b-3p/PGC-1α Pathway.

In hyperlipidemia-induced osteoporosis, bone marrow mesenchymal stem cells (BMSCs) differentiate into more adipocytes than osteoblasts, leading to decreased bone formation. It is vital to elucidate the effects of hyperlipidemia on bone metabolism and seek new agents that regulate adipocyte-osteoblast lineage allocation. CoQ10, a rate-limiting coenzyme of the mitochondrial respiratory chain, has been reported to decrease oxidative stress and lipid peroxidation by functioning as a mitochondrial antioxidant. However, its effect on hyperlipidemia-induced osteoporosis remains unknown. Here, we analyzed the therapeutic mechanisms of CoQ10 on hyperlipidemia-induced osteoporosis by using high-fat diet (HFD)-treated ApoE-/- mice or oxidized low-density lipoprotein (ox-LDL)-treated BMSCs. The serum lipid levels were elevated and bone formation-related markers were decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, which could be reversed by CoQ10. Additionally, PGC-1α protein expression was decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, accompanied by mitochondrial dysfunction, decreased ATP content and overgeneration of reactive oxygen species (ROS), which could also be antagonized by CoQ10. Furthermore, PGC-1α knockdown in vitro promoted ROS generation, BMSC apoptosis, and adipogenic differentiation while attenuating osteogenic differentiation in BMSCs. Mechanistically, it suggested that the expression of PGC1-α protein was increased with miR-130b-3p inhibitor treatment in osteoporosis under hyperlipidemia conditions to improve mitochondrial function. Collectively, CoQ10 alleviates hyperlipidemia-induced osteoporosis in ApoE-/- mice and regulates adipocyte-osteoblast lineage allocation. The possible underlying mechanism may involve the improvement of mitochondrial function by modulating the miR-130b-3p/PGC-1α pathway.

Catalpol ameliorates dexamethasone-induced osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via the activation of PKD1 promoter.

OBJECTIVE: To investigate the effects of CA on glucocorticoid-induced osteoporosis (GIOP) and lucubrate the underlying mechanism of CA via the activation of polycystic kidney disease-1(PKD1) in bone marrow mesenchymal stem cells (BMSCs). METHODS: In vivo, a GIOP model in mice treated with dexamethasone (Dex) was established. Biomechanical, micro-CT, immunofluorescence staining of OCN, ALP and PKD1 and others were severally determined. qRT-PCR and Western blot methods were adopted to elucidate the particular mechanisms of CA on GIOP. In addition, BMSCs cultured in vitro were also induced by Dex to verify the effects of CA. Finally, siRNA and luciferase activity assays were performed to confirm the mechanisms. RESULTS: We found that CA could restore the destroyed bone microarchitecture and increase the bone mass in GIOP mice. CA could also upregulate PKD1 protein expression, reduce oxidative stress, and promote mRNA expression of bone formation-associated markers in GIOP mice. Furthermore, it was also observed that CA reduced oxidative stress and promoted osteogenic differentiation in Dex-induced BMSCs. Mechanically, CA could promote protein expression via increasing the activity of PKD1 promoter. CONCLUSION: This study provides important evidences for CA in the further clinical treatment of GIOP, reveals the activation of PKD1 promoter as the underlying mechanism.

The Wnt/ß-catenin signaling pathway inhibits osteoporosis by regulating the expression of TERT: an in vivo and in vitro study.

Our study was performed to investigate whether the Wingless and int-1 (Wnt) signaling pathway promotes osteogenic differentiation and inhibits apoptosis in bone marrow mesenchymal stem cells (BMSCs) by regulating telomerase reverse transcriptase (TERT) expression. An in vivo model of osteoporosis (OP) in C57BL/6J mice by bilateral ovariectomy (OVX) and an in vitro model of H2O2-induced BMSCs were established separately. Western blotting was used to detect the expression of the pathway-related proteins TERT, ß-catenin, and phosphorylated-glycogen synthase kinase-3beta (p-GSK3ß)/GSK3ß, the osteogenic-related markers osteopontin (OPN), bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (Runx2), and the apoptosis-related indicators B-cell lymphoma-2 (Bcl-2) and BAX. Osteoblastic phenotypes were also evaluated by alkaline phosphatase (ALP) staining and serum ALP activity assays. Osteogenic differentiation phenotypes in mice were verified by H&E staining, micro-CT, and parameter analysis of the femur. Western blotting results showed that the expression of the pathway-related proteins TERT, ß-catenin, p-GSK3ß/GSK3ß was reduced in OVX mice and H2O2-induced BMSCs, accompanied by downregulated protein expression of osteogenic-related markers and antiapoptotic indicators and upregulated protein expression of apoptotic proteins compared to those in the control group. Mechanistic studies showed that the activation of Wnt signaling pathway in BMSCs promoted ß-catenin translocation to the nucleus, as verified by immunofluorescence and facilitated colocalization between ß-catenin and TERT, as verified by double-labeling immunofluorescence, thereby promoting osteogenic differentiation and reducing apoptosis. In summary, our experiments confirmed that the GSK3ß/ß-catenin/TERT pathway could regulate the osteogenic differentiation and apoptosis of BMSCs and that TERT might be a promising target for the future treatment of osteoporosis.

Circ_0114581 promotes osteogenic differentiation of BMSCs via the MiR-155-5p/HNRNPA3 axis.

Osteoporosis (OP) is a common metabolic bone disease characterized by deterioration of bone tissue structure, reduction of bone mass, and susceptibility to fracture. More and new suitable therapeutic targets need to be discovered. The purpose of this study was to explore the ceRNA mechanisms of circRNAs involved in osteoporosis. In this study, a competing endogenous RNA (ceRNA) regulatory network was obtained through the application of OP-related high throughput data sets. Our results provided evidence that HNRNPA3 was involved in the regulation of osteogenic differentiation in BMSCs. Testing of human bone tissues and ovariectomized mice bones proved that its expression level was negatively correlated with OP. The utilization of miRNA mimic or inhibitor proved that miR-155-5p could negatively regulate the expression of HNRNPA3, while overexpression of hsa_circ_0114581 with a circRNA overexpression vector proved that hsa_circ_0114581 could indirectly promoted HNRNPA3 expression and osteogenic differentiation by sponging hsa-miR-155-5p. A serious of luciferase reporter assay experiments further verified the binding site between miR-155-5p and HNRNPA3 and the binding site between miR-155-5p and hsa_circ_0114581. This study proved that the hsa_circ_0114581/hsa-miR-155-5p/HNRNPA3 axis was related with OP. The results reveal valuable insights into the pathogenesis of OP and noncoding RNA markers that may have a treatment role and will help to provide hypotheses for future studies.

High systemic inflammation response index level is associated with an increased risk of lower extremity deep venous thrombosis: a large retrospective study.

BACKGROUND: The association between inflammation and venous thromboembolism (VTE) has attracted increasing research interest. Recently, the systemic inflammation response index (SIRI) has been proposed as a novel inflammatory biomarker, but its potential association with lower extremity deep venous thrombosis (LEDVT) has not been investigated. Thus, this study aimed to explore the association between SIRI and LEDVT risk in a large sample over a 10-year period (2012-2022). METHODS: All hospitalized patients who underwent lower extremity compression ultrasonography (CUS) examinations were consecutively identified from our hospital information system database. Multivariate logistic regression analysis was used to investigate the association between SIRI and LEDVT risk. Sensitivity, restricted cubic spline and subgroup analyses were also performed. RESULTS: In total, 12643 patients were included, and 1346 (10.6%) LEDVT events occurred. After full adjustment, a higher SIRI level was significantly associated with an increased risk of LEDVT (odds ratio [OR] = 1.098, 95% confidence interval [CI]: 1.068-1.128, p < 0.001), and patients in quartile 4 had a 2.563-fold higher risk of LEDVT than those in quartile 1 (95% CI: 2.064-3.182, p < 0.001). A nonlinear relationship was observed (P for nonlinearity < 0.001), with an inflection point of 4.17. Below this point, each unit increase in SIRI corresponded to a 35.3% increase in LEDVT risk (95% CI: 1.255-1.458, p < 0.001). No significant difference was found above the inflection point (OR = 1.015, 95% CI: 0.963-1.069, p = 0.582). Sensitivity and subgroup analyses confirmed the robustness of the association. This association also existed in both distal and proximal LEDVT. CONCLUSION: A High SIRI is significantly associated with an increased risk of LEDVT in hospitalized patients. Given that the SIRI is a readily available biomarker in clinical settings, its potential clinical use deserves further exploration.

A High SIRI is significantly associated with an increased risk of LEDVT in hospitalized patients.The association between SIRI and LEDVT risk was nonlinear, with an inflection point of 4.17.A positive association was observed below the inflection point, but no significant difference was found above this point.

Ganoderma lucidum polysaccharide peptide (GLPP) attenuates rheumatic arthritis in rats through inactivating NF-κB and MAPK signaling pathways.

BACKGROUND: Not many drugs with fewer side effects are available for the treatment of rheumatoid arthritis (RA). Ganoderma lucidum polysaccharide peptide (GLPP) has good immunomodulatory effects, but whether it is effective in managing RA is not clear. PURPOSE: This study was conducted to examine the anti-RA activity and possible mechanisms of GLPP in collagen-induced arthritis (CIA) rats. METHODS: Male Wistar rats were intradermally injected with bovine type II collagen in the tail base to establish the CIA model and were orally administered 100 or 200 mg/kg GLPP for 35 days. Paw thickness, clinical arthritis scores, gait analysis, organ index determination, blood cell counts, micro-CT imaging and pathological staining were performed on the rats. Liver and kidney function were measured by commercial kits, and antibody levels were measured by ELISA kits. RA-related protein levels were detected by Western blotting. RESULTS: GLPP effectively alleviated CIA symptoms and reduced immune organ indexes, antibody levels and systemic organ injury. GLPP decreased the protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, matrix metalloproteinase (MMP)2, MMP9, MMP13, BCL-2, OPN, ß-Catenin, and hypoxia inducible factor (HIF)-1α and increased the protein expression of BAX in the joint tissues of CIA rats. Moreover, GLPP decreased the phosphorylation levels of p65, IκB-α and ERK1/2. CONCLUSION: GLPP effectively alleviated RA symptoms in CIA rats by inhibiting the NF-κB and MAPK pathways. This study suggests a promising therapeutic effect of mushroom-derived polysaccharide peptides on RA.

Association between systemic immune-inflammation index and risk of lower extremity deep venous thrombosis in hospitalized patients: a 10-year retrospective analysis.

Background: The systemic immune-inflammation index (SII), as a novel inflammatory biomarker, has recently attracted attention in cardiovascular disease research. However, the relationship between SII and risk of lower extremity deep venous thrombosis (LEDVT) remains unclear to date. Thus, this study aimed to explore the association in a large sample over a 10-year period (2012-2022). Methods: All hospitalized patients undergoing lower extremity compression ultrasonography (CUS) examination were consecutively screened by searching our hospital information system database. The receiver operating characteristic (ROC) curve analysis was used to identify the optimal cut-off value for high and low SII group. Multivariate logistic regression analyses were performed to investigate the relationship between SII and LEDVT risk. Propensity score matching (PSM), subgroup and sensitivity analyses were also conducted. Moreover, restricted cubic spline (RCS) regression and two-piecewise linear regression models were used to assess the dose-response relationship between natural log transformed SII [ln(SII)] and risk of LEDVT. Results: A total of 16,725 consecutive hospitalized patients were included, and 1,962 LEDVT events occurred. After adjusting for confounding factors, patients in the high SII group (≥ 574.2 × 109/L) showed a 1.740-fold risk of LEDVT (95% CI: 1.546-1.959, P < 0.001), and elevated ln(SII) was associated with a 36.1% increased risk of LEDVT (95% CI: 1.278-1.449, P < 0.001). PSM, subgroup and sensitivity analyses confirmed the robustness of the association. A non-linear relationship was observed (P non-linear < 0.001), with a threshold value of 5.6 × 109/L for all LEDVT events. Above the threshold, each unit increase in ln(SII) had a 1.369-fold higher risk of LEDVT (95% CI: 1.271-1.475, P < 0.001). The association also existed in both distal and proximal LEDVT. Conclusion: Elevated SII is significantly associated with an increased risk of LEDVT in hospitalized patients. Additionally, the association is non-linear and exhibit a threshold effect.

BMSC-derived extracellular vesicles promoted osteogenesis via Axin2 inhibition by delivering MiR-16-5p.

Osteoporosis (OP) is a systemic bone disease caused by an imbalance in osteogenesis and osteoclastic resorption. Extracellular vesicles (EVs)-encapsulated miRNAs from bone mesenchymal stem cells (BMSCs) have been reported to participate in osteogenesis. MiR-16-5p is one of the miRNAs that regulates osteogenic differentiation; however, studies have shown that its role in osteogenesis is controversial. Thus, this study aims to investigate the role of miR-16-5p from BMSC-derived extracellular vesicles (EVs) in osteogenic differentiation and uncover the underlying mechanisms. In this study, we used an ovariectomized (OVX) mouse model and an H2O2-treated BMSCs model to investigate the effects of BMSC-derived EVs and EV-encapsulated miR-16-5p on OP and the underlying mechanisms. Our results proved that the miR-16-5p level was significantly decreased in H2O2-treated BMSCs, bone tissues of OVX mice, and lumbar lamina tissues from osteoporotic women. EVs-encapsulated miR-16-5p from BMSCs could promote osteogenic differentiation. Moreover, the miR-16-5p mimics promoted osteogenic differentiation of H2O2-treated BMSCs, and the effects exerted by miR-16-5p were mediated by targeting Axin2, a scaffolding protein of GSK3ß that negatively regulates the Wnt/ß-catenin signaling pathway. This study provides evidence that EVs-encapsulated miR-16-5p from BMSCs could promote osteogenic differentiation by repressing Axin2.

Anatomic distribution of lower extremity deep venous thrombosis is associated with an increased risk of pulmonary embolism: A 10-year retrospective analysis.

Aims: To investigate the potential relationship between anatomic distribution of lower extremity deep venous thrombosis (LEDVT) and pulmonary embolism (PE). Methods: A retrospective case-control study was performed in patients diagnosed with LEDVT, which were confirmed by bilateral lower extremity compression ultrasonography (CUS) examination. According to the ultrasound reports, thrombus sidedness was categorized as unilateral and bilateral lower extremity, thrombus location was classified into distal and proximal LEDVT. Anatomic distributions of LEDVT were further subdivided depending on the combination of thrombus sidedness and location. Patients with PE were identified using the International Classification of Diseases-10 (ICD-10) codes (I26.0 and I26.9), and divided into PE group and Non-PE group. Univariate and multivariate logistic regression analyses were used to assess the association between anatomic distribution of LEDVT and PE. Sensitivity analyses were also conducted. Results: A total of 2,363 consecutive patients with LEDVT were included, of whom 66.10% and 33.90% were unilateral and bilateral LEDVT, as well as 71.39% and 28.61% were isolated distal and proximal LEDVT, respectively. After the diagnosis of LEDVT, 185 patients (7.83%) developed PE. The proportions of PE ranged between the lowest (4.07%) in unilateral-distal LEDVT and highest (14.55%) in bilateral-proximal LEDVT. Multivariate logistic regression analysis showed that bilateral LEDVT (odds ratios [OR] = 2.455, 95% confidence interval [CI]: 1.803-3.344, P < 0.001) and proximal LEDVT (OR = 1.530, 95% CI: 1.105-2.118, P = 0.010) were risk factors for developing PE. Moreover, unilateral-proximal (OR = 2.129, 95% CI: 1.365-3.320, P = 0.00), bilateral-distal (OR = 3.193, 95% CI: 2.146-4.752, P < 0.001) and bilateral-proximal LEDVT(OR = 3.425, 95% CI: 2.093-5.603, P < 0.001) were significantly associated with an increased risk of PE. Sensitivity analyses also confirmed the robustness of these associations. Conclusion: Patients with unilateral-proximal, bilateral-distal or bilateral-proximal are more likely to suffer from PE than those with unilateral-distal LEDVT.

Potential Anti-Rheumatoid Arthritis Activities and Mechanisms of Ganoderma lucidum Polysaccharides.

Rheumatoid arthritis (RA) is a chronic and autoimmune disease characterized by inflammation, autoimmune dysfunction, and cartilage and bone destruction. In this review, we summarized the available reports on the protective effects of Ganoderma lucidum polysaccharides (GLP) on RA in terms of anti-inflammatory, immunomodulatory, anti-angiogenic and osteoprotective effects. Firstly, GLP inhibits RA synovial fibroblast (RASF) proliferation and migration, modulates pro- and anti-inflammatory cytokines and reduces synovial inflammation. Secondly, GLP regulates the proliferation and differentiation of antigen-presenting cells such as dendritic cells, inhibits phagocytosis by mononuclear macrophages and nature killer (NK) cells and regulates the ratio of M1, M2 and related inflammatory cytokines. In addition, GLP produced activities in balancing humoral and cellular immunity, such as regulating immunoglobulin production, modulating T and B lymphocyte proliferative responses and cytokine release, exhibiting immunomodulatory effects. Thirdly, GLP inhibits angiogenesis through the direct inhibition of vascular endothelial cell proliferation and induction of cell death and the indirect inhibition of vascular endothelial growth factor (VEGF) production in the cells. Finally, GLP can inhibit the production of matrix metalloproteinases and promote osteoblast formation, exerting protective effects on bone and articular cartilage. It is suggested that GLP may be a promising agent for the treatment of RA.

Anti-Postmenopausal osteoporosis effects of Isopsoralen: A bioinformatics-integrated experimental study.

Isopsoralen (IPRN), which comes from the fruit of Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proven to be effective for the treatment of osteoporosis (OP). However, the mechanisms underlying IPRN's anti-OP effects, especially the anti-postmenopausal osteoporosis (PMOP) effects, remain indistinct. Thus, this study aimed to investigate the effects and mechanisms of IPRN's anti-PMOP activity. In this study, the bioinformatics results predicted that IPRN could resist PMOP by targeting EGFR, AKT1, SRC, CCND1, ESR1 (ER-α), AR, PGR, BRCA1, PTGS2, and IGF1R. An ovariectomized (OVX) mice model and a H2 O2 -induced bone marrow mesenchyml stem cells (BMSCs) model confirmed that IPRN could inhibit the bone loss induced by OVX in mice and promote the osteogenic differentiation in H2 O2 -induced BMSCs by inhibiting oxidative stress and apoptosis. Moreover, IPRN could significantly produce the above effects by upregulating ESR1. IPRN might be a therapeutic agent for PMOP by acting as an estrogen replacement agent and a natural antioxidant.

The Widowhood Effect on Mortality in Older Patients with Hip Fracture.

Objective: Widowed people have increased mortality than married people of the same age, a phenomenon known as the widowhood effect. This study aimed to investigate whether this effect exists in older patients with hip fracture. Methods: Using our own hip fracture database, a total of 1101 hip fracture patients were consecutively included from January 2014 to December 2021. Marital status was stratified as married (n = 793) and widowed (n = 308). Patients survival status was obtained from medical records or telephone follow-ups, and the outcomes were all-cause mortality at 30 days, 1 year and at latest follow-up. Univariate and multivariate Cox proportional hazard models were used to assess the association between marital status and mortality, and subgroup analyses according to sex were also conducted. Results: Compared with married patients, widowed patients were more likely to be older, female and intertrochanteric fracture, and were less likely to be urban area, smoking, drinking, and surgical treatment (P < 0.05). After a median follow-up of 37.1 months, the 30-day mortality was 4.3% (n = 47), 1-year mortality was 19.3% (n = 178), and total mortality was 34.2% (n = 376). Multivariate Cox analysis showed that widowed marital status remained an independent risk factor for 1-year mortality (HR = 1.437, 95% CI: 1.054-1.959, P = 0.022), and total mortality (HR = 1.296, 95% CI: 1.038-1.618, P = 0.022), whereas this association was not found in 30-day mortality (HR = 1.200, 95% CI: 0.607-2.376, P = 0.599). Moreover, subgroup analyses also found that the widowhood effect on mortality was present in both male and female. Conclusion: Widowed marital status seems to be an independent risk factor for long-term mortality in older patients with hip fracture.

Muscular Calf Vein Thrombosis Is Associated With Increased 30-Day Mortality But Not 90-Day Mortality in Older Patients With Hip Fracture.

Calf deep vein thrombosis (DVT) is common in patients with hip fractures. However, studies on whether calf DVT has an impact on the prognosis are limited. This retrospective cohort study explored the association between calf DVT and 30-day and 90-day all-cause mortality in older patients with hip fractures. A total of 564 consecutive patients who underwent ultrasound examination were identified from our hip fracture database and categorized into patients with calf DVT (axial DVT, muscular DVT) and no DVT. Of these, 86 patients (15.2%) had ultrasound-confirmed calf DVT, including 66 patients with muscular DVT, and 20 patients with axial DVT. The 30-day and 90-day all-cause mortality were 2.5% and 6.0%, respectively. Multivariate Cox analysis showed that calf DVT was significantly associated with an increased risk of 30-day mortality (hazard ratio [HR] 3.21, 95% confidence interval [CI] 1.05 to 9.84, p = 0.04), but this risk relationship did not persist at 90-day follow-up (HR 1.59, 95% CI 0.69 to 3.71, p = 0.28). When calf DVT was further categorized, muscular DVT remained an independent risk factor for 30-day mortality (HR 3.95, 95% CI 1.18 to 13.15, p = 0.03), whereas this relationship was not found in axial DVT (HR 1.79, 95% CI 0.21 to 15.02, p = 0.59). In conclusion, calf DVT, especially muscular calf DVT but not axial DVT, is independently associated with an increased risk of 30-day mortality in older patients with hip fracture, but this risk relationship did not persist at 90-day follow-up.

The integrative analysis of competitive endogenous RNA regulatory networks in osteoporosis.

Osteoporosis (OP) is a common bone disease of old age resulting from the imbalance between bone resorption and bone formation. CircRNAs are a class of endogenous non-coding RNAs (ncRNAs) involved in gene regulation and may play important roles in the development of OP. Here, we aimed to discover the OP­related circRNA-miRNA-mRNA (ceRNA) network and the potential mechanisms. Six microarray datasets were obtained from the GEO database and the OP­related differentially expressed genes (DEGs), circRNAs (DECs), and miRNAs (DEMs) were screened out from these datasets. Then, combined with the prediction of the relationships between DEGs, DEMs, and DECs, a ceRNA network containing 7 target circRNAs, 5 target miRNAs, and 38 target genes was constructed. Then the RNA-seq verification by using total RNAs isolated from the femurs of normal and ovariectomized Wistar rats indicated that MFAP5, CAMK2A, and RGS4 in the ceRNA network were closely associated with osteoporosis. Function enrichment analysis indicated that the target circRNAs, miRNAs, and genes were involved in the process of MAPK cascade, hormone stimulus, cadherin binding, rRNA methyltransferase, PI3K-Akt signaling pathway, and Vitamin digestion and absorption, etc. Then a circRNA-miRNA-hub gene subnetwork was constructed and the qRT-PCR analysis of human bone tissues from the femoral head was used to confirm that the transcription of hsa_circR_0028877, hsa_circR_0082916, DIRAS2, CAMK2A, and MAPK4 showed a significant correlation with osteogenic genes. Besides, the two axes of hsa_circR_0028877/hsa-miR-1273f/CAMK2A and hsa_circR_0028877/hsa-miR-1273f/DIRAS2 conformed to be closely associated with OP. Additionally, by constructing a drug-target gene network, RKI-1447, FRAX486, Hyaluronic, and Fostamatinib were identified as therapeutic options for OP. Our study revealed the potential links between circRNAs, miRNAs, and mRNAs in OP, suggesting that the ceRNA mechanism might contribute to the occurrence of OP.

Phosphocreatine Promotes Osteoblastic Activities in H2O2-Induced MC3T3-E1 Cells by Regulating SIRT1/FOXO1/PGC-1α Signaling Pathway.

BACKGROUND: Osteoporosis, characterized by bone loss, usually occurs with the increased bone resorption and decreased bone formation. H2O2-induced MC3T3-E1 cells are commonly used for the study of osteoblastic activities, which play a crucial role in bone formation. OBJECTIVE: This study aimed to investigate the effects of Phosphocreatine (PCr) on the osteoblastic activities in H2O2-induced MC3T3-E1 cells and elaborate on the possible molecular mechanism. METHODS: The Osteoprotegerin (OPG)/Receptor Activator of NF-κB Ligand (RANKL) ratio and osteogenic markers were detected to investigate the effects of PCr on osteoblastic activities, and the osteoblastic apoptosis was detected using Hochest staining. Moreover, oxidative stress, Adenosine Triphosphate (ATP) generation and the expression of Sirtuin 1 (SIRT1), Forkhead Box O 1 (FOXO1) and Peroxisome Proliferator-Activated Receptor Γ Coactivator-1α (PGC-1α) were also examined to uncover the possible molecular mechanism in H2O2-induced MC3T3-E1 cells. RESULT: The results showed that PCr promoted the osteoblastic differentiation by increasing the expression levels of osteogenic markers of Alkaline Phosphatase (ALP) and Runt-related transcription factor 2 (Runx2), as well as increased the OPG/RANKL ratio and suppressed the osteoblastic apoptosis in H2O2-induced MC3T3-E1 cells. Moreover, treatment with PCr suppressed reactive oxygen species (ROS) over-generation and promoted the ATP production as well as increased the PGC-1α, FOXO1 and SIRT1 protein expression levels in H2O2-induced MC3T3-E1 cells. CONCLUSION: PCr treatment could promote osteoblastic activities via suppressing oxidative stress and increasing the ATP generation in H2O2-induced MC3T3-E1 cells. In addition, the positive effects of PCr on osteoblasts might be regulated by SIRT1/FOXO1/ PGC-1α signaling pathway.

Design and application of a novel patient-specific 3D printed drill navigational guiding template in percutaneous thoracolumbar pedicle screw fixation: A cadaveric study.

The conventional surgical method of percutaneous pedicle screw fixation (PPSF) mainly uses X-ray fluoroscopy guidance to target the vertebral pedicle for screw placement. This study aimed to explore the feasibility of establishing a personalized drill guide template for PPSF based on a three-dimensional (3D) printing technique and to evaluate the accuracy and safety of the method for assisting screw insertion in cadaveric specimens. The T3-L3 trunk cadaveric specimens from six adults were subject to a computed tomography (CT) scan in the prone position. A three-dimensional model containing the back skin contour was reconstructed. A bilateral ideal pedicle screw in the T6-L1 segment was designed. Then, the reverse templates were designed. The two templates were fused and printed into an individualized guide template. PPSF was performed under the assistance of the guide template, and the CT scan was taken postoperatively to access the screw position. Ninety-six pedicle screws were successfully placed on the bilateral vertebral body of the T6-L1 segment with the assistance of a guide template. The guide plate was not loosened or displaced when operated by a single hand, and the operation time was 24.6 ± 7.9 s. The axial CT images after puncture indicated that in 96 puncture needles, 90 needles were grade I and 6 were grade II, with a puncture accuracy rate of 98.6%. In conclusion, an individualized PPSF navigation template was developed using Mimics software and 3D printing prototyping, which improved the accuracy of PPSF in cadaveric specimens.

Incidence, Prevalence, and Analysis of Risk Factors for Surgical Site Infection After Lumbar Fusion Surgery: ≥2-Year Follow-Up Retrospective Study.

PURPOSE: Surgical site infection (SSI) in spine surgery remains a significant cause of morbidity and prolonged hospitalization. We intended to document our experience in our center and to highlight possible factors influencing SSI in posterior lumbar fusion surgery. METHODS: Between June 2015 and March 2017, 448 consecutive patients with lumbar degenerative disease who underwent classic open transforaminal lumbar interbody fusion were enrolled in the study. We divided the patients into the SSI group and the non-SSI group and compared their patient-specific and procedure-specific factors. Univariate and multiple logistic regression analyses were performed to determine risk factors. RESULTS: There was a significant difference between groups in age (P = 0.001), body mass index (P < 0.001), subcutaneous fat thickness (P < 0.001), preoperative American Society of Anesthesiologists (ASA) score (P < 0.001), postoperative hemoglobin (P = 0.003), preoperative serum albumin (P < 0.001), operative time (P < 0.001), operated levels (P < 0.001), postoperative drainage (P = 0.004), time of draining (P < 0.001) and late-presenting dural tear (P = 0.008). Logistic regression analysis of these differences showed that thicker subcutaneous fat thickness, higher preoperative ASA score, lower preoperative serum albumin, and longer time of draining were significantly related to SSI (P < 0.05). CONCLUSIONS: The risk factors for SSI after lumbar fusion surgery are multifactorial. These data should provide a step toward the development of quality improvement measures aimed at reducing complications in high-risk patients. These factors may prove useful for patient counseling and for surgical planning.

Luteolin attenuates glucocorticoid-induced osteoporosis by regulating ERK/Lrp-5/GSK-3ß signaling pathway in vivo and in vitro.

Glucocorticoid-induced osteoporosis (GIO) is a secondary osteoporosis with extensive use of glucocorticoids (GCs). GCs can increase bone fragility and fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant activity, but the effects of LUT on GIO still remain unclear. This study aimed to investigate the effects of LUT on GIO both in vivo and in vitro and elaborate the potential molecular mechanisms. LUT increased the superoxide dismutase activity, glutathione level and decreased reactive oxygen species (ROS) level and lactate dehydrogenase release in GIO. Meanwhile, LUT decreased caspase-3, caspase-9, and Bax protein expressions and increased Bcl-2 protein expression in GIO. LUT increased the ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB Ligand (RANKL) messenger RNA (mRNA) expression and mRNA expression levels of osteogenic markers, including runt-related transcription factor 2, osterix, collagen type I, and osteocalcin. LUT also enhanced the extracellular signal-regulated kinases (ERK) phosphorylation, glycogen synthase kinase 3ß (GSK-3ß) phosphorylation, mRNA expression levels of lipoprotein-receptor-related protein 5 (Lrp-5) and ß-catenin. Further study revealed that Lrp-5 small interfering RNA (siRNA )and ERK-siRNA reduced the effects of LUT on GSK-3ß phosphorylation, alkaline phosphatase (ALP) activity and the ratio of OPG/RANKL mRNA expression. Moreover, ERK-siRNA decreased Lrp-5 mRNA expression in vitro. These results indicated that LUT promoted proliferation by attenuating oxidative stress and promoted osteoblastic differentiation by regulating the ERK/Lrp-5/GSK-3ß pathway in GIO. This study may bring to light the possible mechanisms involved in the action of LUT in GIO treatment, and benefit for further research on GIO.

Protective effects of dioscin against cartilage destruction in a monosodium iodoacetate (MIA)-indcued osteoarthritis rat model.

BACKGROUND: Osteoarthritis (OA) is a disabling disease of joint with no clear treatment. The finding of medicine be of benefit to joint is an important topic for osteoarthritis prevention and treatment. The present study was designed to explore the therapeutic effects and possible underlying mechanism of dioscin, a natural steroidal saponin, on osteoarthritis. METHODS: OA models were created via intra-joint injection of monosodium iodoacetate (MIA) in rats. After the administration of dioscin, the effects of dioscin were estimated with western blotting, qRT-PCR and histologic staining. RESULTS: The results showed that dioscin exerted cartilage and extracelluar matrix (ECM) protective effects via suppressing ER-stress, oxidative stress, apoptosis and inflammation. More significantly, it also ameliorated the progress of OA via inhibiting Wnt/ß-catenin pathway and up-regulating PPAR-γ expression. CONCLUSION: Our work showed the good protective effects of dioscin on MIA-induced OA for the first time. Dioscin is a promising drug on OA treatment although further researches are needed in the future.