IGF2BP2, an RNA-binding protein regulates cell proliferation and osteogenic differentiation by stabilizing SRF mRNA.

Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by complex mechanisms. The roles in cell proliferation and OGD of RNA-binding proteins in the insulin-like growth factor 2 mRNA-binding protein (IGF2BP) family remain unclear. To elucidate this, we examined the differential expression of IGF2BP2 in OGD and osteoporosis, and the expression profile of IGF2BP2-binding RNA in vitro. We screened the GEO database for differential expression of IGF2BP in OGD and osteoporosis, and verified the RNAs interacting with IGF2BP2 via RNA immunoprecipitation sequencing assays. The proliferation and OGD of IGF2BP2- and serum response factor (SRF)-treated cells, and their regulatory mechanisms, were examined. IGF2BP2 was differentially expressed in OGD and osteoporosis. The RNA immunoprecipitation sequencing assay identified all of the RNAs that bind with IGF2BP2, and revealed SRF as a target of IGF2BP2. IGF2BP2 and SRF inhibition impaired MC3T3-E1 cell growth but promoted OGD. The mRNA stability analysis revealed that IGF2BP2 enhanced SRF mRNA stability against degradation. In summary, IGF2BP2 is a potential biomarker and therapeutic target for osteoporosis and OGD.

UHRF1 associated with osteogenic differentiation of MSCs contributes to osteosarcoma progression and has clinical prognostic impact in osteosarcoma.

Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) can mediate DNA methylation and histone modifications in the epigenetic regulation of gene expression, stem cell differentiation and tumorigenesis. Here, we analyzed the differentially expressed mRNAs (DEmRNAs) in osteogenesis differentiation of MSCs and osteosarcoma. We identified UHRF1 as the co-DEmRNA to regulate the osteogenesis differentiation of MSCs and osteosarcoma. Moreover, we determined that the functions and pathways of UHRF1 in osteosarcoma. This finding indicates that UHRF1 is closely associated with metastasis and recurrence in osteosarcoma. Based on this finding, we derived a risk signature using UHRF1. In conclusion, UHRF1 is a crucial role in the malignant progression of osteosarcoma and are potentially useful for osteosarcoma progression treatment strategy development.

Role of long non-coding RNA H19 in the development of osteoporosis.

BACKGROUND: Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example. RESULTS: A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis. CONCLUSION: The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.

Long non-coding RNAs in osteoporosis: from mechanisms of action to therapeutic potential.

Osteoporosis is a clinical disease characterized by decreased bone density due to a disrupted balance between bone formation and resorption, which increases fracture risk and negatively affects the quality of life of a patient. LncRNAs are RNA molecules over 200 nucleotides in length with non-coding potential. Many studies have demonstrated that numerous biological processes involved in bone metabolism are affected. However, the complex mechanisms of action of lncRNAs and their clinical applications in osteoporosis have not yet been fully elucidated. LncRNAs, as epigenetic regulators, are widely involved in the regulation of gene expression during osteogenic and osteoclast differentiation. LncRNAs affect bone homeostasis and osteoporosis development through different signaling pathways and regulatory networks. Additionally, researchers have found that lncRNAs have great potential for clinical application in the treatment of osteoporosis. In this review, we summarize the research results on lncRNAs for clinical prevention, rehabilitation treatment, drug development, and targeted therapy for osteoporosis. Moreover, we summarize the regulatory modes of various signaling pathways through which lncRNAs affect the development of osteoporosis. Overall, these studies suggest that lncRNAs can be used as novel targeted molecular drugs for the clinical treatment of osteoporosis to improve symptoms.

Risk Factors in Patients with Low Back Pain Under 40 Years Old: Quantitative Analysis Based on Computed Tomography and Magnetic Resonance Imaging mDIXON-Quant.

Purpose: While low back pain (LBP) constitutes a global life disorder cause, the contribution of paraspinal muscles to its pathogenicity remains elusive. We characterized the paraspinal muscles of patients with LBP using lumbar three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) mDIXON-Quant, and evaluated the risk factors combined with clinical data. Methods: A retrospective study involving 181 patients (10-40 years) who underwent lumbar 3D-CT and MRI mDIXON from January 1, 2021 to December 31, 2022, and divided into normal, non-chronic LBP [non-CLBP], and CLBP groups. Clinical data, paraspinal muscle cross-sectional area, Hounsfield unit for CT values, and fat fraction derived from mDIXON-Quant were compared. Three readers analyzed the images independently; intra- and interobserver agreement was measured. Spearman analysis and multiple logistic regression were used to analyze the correlation between clinical data, radiologic and paraspinal muscle parameters. A nomogram was constructed for individualized prediction. Results: Correlation analysis revealed that body mass index, visual analog scale score, Pfirrmann grade, annulus fibrosus tear, lumbar lordosis (LL), and Modic changes correlated with LBP (all P<0.05). The Pfirrmann grade and annulus fibrosus tear showed positive correlation (r=0.673, 0.559), whereas LL was negatively correlated (r=-0.469). The multifidus CT values were negatively correlated with LBP at L4-5/L5-S1; the multifidus fat fraction was positively correlated at L4-5/L5-S1 (r=0.734, r=0.584, P<0.001). The multiple logistic regression showed that L4-5 multifidus fat fraction (P=0.046, OR=1.167), Pfirrmann grade (P=0.017, OR=0.063), LL (P=0.002, OR=0.828) and annulus fibrosus tear (P=0.005, OR=0.024) were risk factors for predicting LBP in the non-CLBP group; in the CLBP group, BMI (P=0.048 OR=1.225), L4-5 multifidus fat fraction (P=0.001 OR=1.299), LL (P=0.003, OR=0.841) and Pfirrmann classification (P=0.009, OR=0.046) were risk factors. Conclusion: BMI, L4-5 multifidus fat fraction, LL, and Pfirrmann grade are risk factors for CLBP in patients under 40; whereas annulus fibrosus tear is an independent risk factor for non-CLBP, nomograms derived from these parameters can help predict LBP and MRI mDIXON-Quant is recommended for quantitatively analyzing paraspinal muscle fat infiltration.

Ginsenoside Compound K Ameliorates Osteoarthritis by Inhibiting the Chondrocyte Endoplasmic Reticulum Stress-Mediated IRE1α-TXNIP-NLRP3 Axis and Pyroptosis.

Osteoarthritis (OA) is a common joint disease, and studies have reported that the endoplasmic reticulum stress (ERS) in chondrocytes caused by the cartilage tissue damage could mediate the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes through inositol-requiring enzyme 1 alpha (IRE1α) and thioredoxin interacting protein (TXNIP). Ginsenoside compound K (CK) has an inhibitory effect on IRE1α activation. However, the role of IRE1α-TXNIP and its interaction with CK are still unclear. In this study, we examined the role and mechanism of action of CK in OA. We found that CK ameliorated OA and ERS in IL-1ß-treated chondrocytes and a monoiodoacetate-induced rat OA model. The effect of CK on inflammation, pyroptosis, and ERS was blocked by the ERS inducer tunicamycin. In conclusion, CK hindered OA progression by inhibiting the ERS-IRE1α-TXNIP-NLRP3 axis. Overall, our data indicate that CK could be useful in the treatment of OA and other chronic inflammatory diseases.

Actin polymerization inhibition by targeting ARPC2 affects intestinal stem cell homeostasis.

Background: The rapid turnover of the intestinal epithelium is driven by the proliferation and differentiation of intestinal stem cells (ISCs). The dynamics of the F-actin cytoskeleton are critical for maintaining intercellular force and the signal transduction network. However, it remains unclear how direct interference with actin polymerization impacts ISC homeostasis. This study aims to reveal the regulatory effects of the F-actin cytoskeleton on the homeostasis of intestinal epithelium, as well as the potential risks of benproperine (BPP) as an anti-tumor drug. Methods: Phalloidin fluorescence staining was utilized to test F-actin polymerization. Flow cytometry and IHC staining were employed to discriminate different types of intestinal epithelial cells. Cell proliferation was assessed through bromo-deoxyuridine (BrdU) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. The proliferation and differentiation of intestinal stem cells were replicated in vitro through organoid culture. Epithelial migration was evaluated through BrdU pulse labeling and chasing in mice. Results: The F-actin content was observed to significantly increase as crypt cells migrated into the villus region. Additionally, actin polymerization in secretory cells, especially in Paneth cells (PCs), was much higher than that in neighboring ISCs. Treatment with the newly identified actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor BPP led to a dose-dependent increase or inhibition of intestinal organoid growth in vitro and crypt cell proliferation in vivo. Compared with the vehicle group, BPP treatment decreased the expression of Lgr5 ISC feature genes in vivo and in organoid culture. Meanwhile, PC differentiation derived from ISCs and progenitors was decreased by inhibition of F-actin polymerization. Mechanistically, BPP-induced actin polymerization inhibition may activate the Yes1-associated transcriptional regulator pathway, which affects ISC proliferation and differentiation. Accordingly, BPP treatment affected intestinal epithelial cell migration in a dose-dependent manner. Conclusion: Our findings indicate that the regulation of cytoskeleton reorganization can affect ISC homeostasis. In addition, inhibiting ARPC2 with the Food and Drug Administration-approved drug BPP represents a novel approach to influencing the turnover of intestinal epithelial cells.

Trafficking and effect of released DNA on cGAS-STING signaling pathway and cardiovascular disease.

Evidence from clinical research and animal studies indicates that inflammation is an important factor in the occurrence and development of cardiovascular disease (CVD). Emerging evidence shows that nucleic acids serve as crucial pathogen-associated molecular patterns (PAMPs) or non-infectious damage-associated molecular patterns (DAMPs), are released and then recognized by pattern recognition receptors (PRRs), which activates immunological signaling pathways for host defense. Mechanistically, the released nucleic acids activate cyclic GMP-AMP synthase (cGAS) and its downstream receptor stimulator of interferon genes (STING) to promote type I interferons (IFNs) production, which play an important regulatory function during the initiation of an innate immune response to various diseases, including CVD. This pathway represents an essential defense regulatory mechanism in an organism's innate immune system. In this review, we outline the overall profile of cGAS-STING signaling, summarize the latest findings on nucleic acid release and trafficking, and discuss their potential role in CVD. This review also sheds light on potential directions for future investigations on CVD.

Mesenchymal stem cell-seeded porous tantalum-based biomaterial: A promising choice for promoting bone regeneration.

Porous tantalum-based biomaterial is a novel tissue engineering material widely used in repairing bone defects due to its corrosion resistance, low elastic modulus, high friction coefficient, and excellent biocompatibility. Bone marrow-derived mesenchymal stem cells (BMSCs), a type of pluripotent stem cell, can travel from their original ecological niche to bone injury sites, where they differentiate into osteoblasts and osteocytes. Multiple factors regulate the proliferation, migration, and differentiation of BMSCs. In recent years, the regulatory effects of porous tantalum on BMSCs have been widely studied. Hence, in this study, we reviewed the characteristics of porous tantalum-based biomaterials and the mechanism of action of their regulatory effects on BMSCs. Further, we discuss the feasibility of seeding BMSCs in porous tantalum-based biomaterials for use in tissue repair.

Undifferentiated pleomorphic sarcoma of the lateral thigh with KRAS/NF1 co-mutation recurred after repetitive surgical resection: A case report and review of the literature.

Undifferentiated pleomorphic sarcoma (UPS), a rare soft tissue sarcoma subtype, mainly occurs in the deep parts of the limbs and trunk, observed as rapidly growing painless lumps, rarely located under the skin or protrudes from the skin surface. The risk of recurrence and metastasis is associated with multiple factors. Mutation of tumor gene, tumor occurrence, location and depth of invasion, and tumor size have great influence on prognosis. In this study, we described a case of UPS with KRAS/NF1 co-mutation. This case had undergone UPS extended resection for four times combined with chemotherapy in another hospital. The resection area was more than 3 cm, and tumor relapsed after all operations. This time, the tumor protruded from the left lateral surface with ulceration and infection. Due to multiple surgeries, the anatomy of the lateral femoral vessels has been seriously damaged. We performed expanded tumor resection and adjacent flap transfer repair; meanwhile, vacuum sealing drainage (VSD)-negative pressure closed the drainage, and the patient recovered well after surgery. After surgery, the patient was transferred to the Department of Oncology for chemotherapy. There was no recurrence after 6 months of follow-up. Gene mutation plays an important role in UPS recurrence and metastasis. At the same time, occurrence and location, depth, and size of UPS have great influence on the prognosis. Deeper exploration and expanded resection are important for the prognosis of UPS.

Differentiation of Thyroid Nodules (C-TIRADS 4) by Combining Contrast-Enhanced Ultrasound Diagnosis Model With Chinese Thyroid Imaging Reporting and Data System.

Objectives: To establish a contrast-enhanced ultrasound (CEUS) diagnostic schedule by CEUS analysis of thyroid nodules of C-TIRADS 4. To establish a CEUS-TIRADS diagnostic model to differentiate thyroid nodules (C-TIRADS 4) by combining CEUS with Chinese thyroid imaging reporting and data system (C-TIRADS). Methods: A total of 228 thyroid nodules (C-TIRADS 4) were estimated by CEUS. The arrival time, enhancement degree, enhancement homogeneity, enhancement pattern, enhancement ring, and wash-out time were analyzed in CEUS for all of the nodules. Multivariate factors logistic analysis was performed and a CEUS diagnostic schedule was established. If the nodule had a regular hyper-enhancement ring or got a score of less than 2 in CEUS analysis, CEUS-TIRADS subtracted 1 category. If the nodule got a score of 2 in the CEUS schedule, the CEUS-TIRADS category remained the same as before. If the nodule got a score of more than 2 in the CEUS schedule, CEUS-TIRADS added 1 category. When it reflected an absent enhancement in CEUS, the nodule was judged as CEUS-TIRADS 3. All of the C-TIRADS 4 nodules were re-graded by CEUS-TIRADS. We then compare the diagnosis performance of C-TIRADS, CEUS, and CEUS-TIRADS by sensitivity, specificity, and accuracy. Results: Among the 228 C-TIRADS 4 nodules, 69 were determined as C-TIRADS 4a, 114 were C-TIRADS 4b, and 45 were C-TIRADS 4c. The sensitivity, specificity, and accuracy of C-TIRADS were 93.1%, 55.3%, and 74.6% respectively. The area under the curve was 0.753. Later arrival time, hypo-enhancement, heterogeneous enhancement, centripetal enhancement, and rapid washout were risk factors of malignancy in multivariate analysis. The sensitivity, specificity, and accuracy of CEUS were 78.7%, 87.5%, and 83.3% respectively. The area under the curve was 0.803. By CEUS-TIRADS diagnostic model combining CEUS with C-TIRADS, a total of 127 cases were determined as malignancy (111 were malignant and 16 were benign) and 101 were diagnosed as benign ones (5 were malignant and 96 were benign). The sensitivity, specificity, and accuracy of CEUS-TIRADS were 95.7%, 85.7%, and 92.1% respectively. The area under the curve was 0.916. The diagnostic performance of CEUS-TIRADS was significantly better than CEUS and C-TIRADS. The difference was statistically significant (P<0.05). Conclusions: The diagnostic schedule of CEUS could get better diagnostic performance than US in the differentiation of thyroid nodules. The CEUS-TIRADS combining CEUS analysis with C-TIRADS could make up for the deficient sensibility of C-TIRADS, showing a better diagnostic performance than US and CEUS.

Systematic Analysis of the Expression Profile and Prognostic Significance of the IGF2BP Family in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), the most common type of lung cancer associated with poor prognosis, has become a major health problem. IGF2BPs are types of N6-methyladenosine reader proteins, comprising IGF2BP1, IGF2BP2, and IGF2BP3, that promote LUAD progression. However, the expression profiles and prognostic value of IGF2BPs in LUAD remain unclear. OBJECTIVE: This study aimed to analyze the expression profiles and prognostic significance of the IGF2BP family in lung adenocarcinoma. METHODS: In this study, we included tissue data of LUAD patients and normal or para-carcinoma from the TCGA database and the GTEx project. Using survival analysis, Kaplan-Meier curves, and Cox proportional hazards model, we analyzed the expression profiles and prognostic significance of the IGF2BP family. RESULTS: Patients with high expression levels of IGF2BPs showed a significant association with poor overall survival (p < 0.05). Moreover, the somatic mutation rates of IGF2BP1, IGF2BP2, and IGF2BP3 were determined as 2.65, 1.59, and 1.76%, respectively, by investigating the genetic mutation. In addition, there were significant associations between TMB and IGF2BP family expression profiles, which positively correlated with the expression of PD-1 (p < 0.05). Cox proportional hazard model for LUAD showed the risk score for IGF2BP1, p-TNM stage, and so forth, all independent prognostic indicators for LUAD patients. Finally, the co-expression genes were obtained to build a PPI network and analyze the hub genes of the IGF2BP family. CONCLUSION: Our study provides further insights into the role of the IGF2BP family in LUAD and identifies 10 genes that may be associated with IGF2BPs in LUAD patients.

Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration.

Osteogenic differentiation and bone regeneration are complex processes involving multiple genes and multiple steps. In this review, we summarize the effects of the long noncoding RNA (lncRNA) H19 on osteogenic differentiation.Osteogenic differentiation includes matrix secretion and calcium mineralization as hallmarks of osteoblast differentiation and the absorption of calcium and phosphorus as hallmarks of osteoclast differentiation. Mesenchymal stem cells (MSCs) form osteoprogenitor cells, pre-osteoblasts, mature osteoblasts, and osteocytes through induction and differentiation. lncRNAs regulate the expression of coding genes and play essential roles in osteogenic differentiation and bone regeneration. The lncRNA H19 is known to have vital roles in osteogenic induction.This review highlights the role of H19 as a novel target for osteogenic differentiation and the promotion of bone regeneration.

Long Noncoding RNA GAS5: A New Factor Involved in Bone Diseases.

Long noncoding RNAs (lncRNAs), as an important type of RNA encoded in the human transcriptome, have shown to regulate different genomic processes in human cells, altering cell type and function. These factors are associated with carcinogenesis, cancer metastasis, bone diseases, and immune system diseases, among other pathologies. Although many lncRNAs are involved in various diseases, the molecular mechanisms through which lncRNAs contribute to regulation of disease are still unclear. The lncRNA growth arrest-specific 5 (GAS5) is a key player that we initially found to be associated with regulating cell growth, differentiation, and development. Further work has shown that GAS5 is involved in the occurrence and prognosis of bone diseases, such as osteoporosis, osteosarcoma, and postosteoporotic fracture. In this review, we discuss recent progress on the roles of GAS5 in bone diseases to establish novel targets for the treatment of bone diseases.