Feng Zheng

Background: Modic changes refer to bone marrow alterations beneath vertebral endplates and are potentially linked to infection, trauma, disc degeneration, scoliosis, and other pathological conditions. Systematic evaluations of their incidence and associated risk factors in the lumbar spine are lacking. This study aimed to analyze and evaluate the incidence and risk factors of Modic changes in lumbar spine disorders.Methods: A comprehensive systematic review was conducted using Web of Science, PubMed, Cochrane Library, and Embase databases. Eligible studies reported the incidence and associated risk factors of Modic changes in the lumbar spine. Data were extracted and systematically analyzed from the selected studies, and meta-analyses were conducted employing random or fixed effects models.Results: Twenty-five studies were included in the meta-analysis. The overall incidence of Modic changes was 35%. Six risk factors were identified and quantitatively assessed. Strong evidence supported the association of endplate changes (OR=3.56; 95% CI=2.00 to 6.32; p<0.0001); moderate evidence supported the association of age (OR=4.01; 95% CI=1.37 to 6.65; p=0.003), disc degeneration (OR=8.54; 95% CI=1.98 to 36.73; p=0.004), and lumbar lordosis angle (OR=-4.14; 95% CI=-6.79 to -1.49; p=0.002); minor evidence supported the association of spondylolisthesis (OR=2.00; 95% CI=1.12 to 3.58; p=0.02) and physical labor (OR=1.81; 95% CI=1.08 to 3.04; p=0.03) with the occurrence of Modic changes in the lumbar spine. No significant associations were found to support body mass index, sex, disc herniation, smoking, distributional segmentation, or sacral slope angle as risk factors for Modic changes in the lumbar spine.Conclusion: Modic changes occur in 35% of lumbar spine cases, with advanced age, disc degeneration, endplate changes, spondylolisthesis, reduced anterior lumbar lordosis angles, and participation in physical labor identified as associated risk factors.

Osteoporosis (OP) is a prevalent skeletal disorder characterized by an imbalance between bone resorption and bone formation, resulting in a significant global burden. Previous research utilizing bioinformatics analysis has identified MAP4K2, SPI1, and CTSD as hub genes associated with OP. In this current investigation, we have successfully established a differential expression system of MAP4K2, SPI1, and CTSD in rat bone marrow mesenchymal stem cells (BMSCs) through transfection techniques. Additionally, the CCK-8 assay was employed to assess cell proliferation, while the alkaline phosphatase (ALP) activity assay and ALP staining assay were utilized to evaluate osteogenic differentiation. Alizarin red staining was employed to detect mineralization of BMSCs. Furthermore, the expression of relevant genes and molecules associated with the MAPK signaling pathway, autophagy, and apoptosis in the sera of rat BMSCs were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The purpose of this study was to preliminarily investigate whether MAP4K2, SPI1, and CTSD have an effect on the osteogenic capacity of rat BMSCs and whether these genes, when differentially expressed, affect the expression of related genes in the MAPK, autophagy, and apoptosis signaling pathways and thus the osteogenic function of BMSCs. In summary, the findings of this study indicate that MAP4K2 and CTSD exert significant influence on the proliferation, osteogenic differentiation, and mineralization processes of rat BMSCs cells. Furthermore, these proteins may contribute to the development of OP through their involvement in the regulation of autophagy and apoptosis. Conversely, our investigation did not reveal any discernible impact of SPI1 on OP-related phenotypes. Consequently, this research serves as a fundamental basis for further exploration of potential therapeutic targets for the treatment of OP.

Objective: Osteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in‐depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single‐cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease.Methods: Single cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP‐counter, and ssGSEA algorithms. Real‐time fluorescence quantitative PCR (RT‐qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults.Results: In OP samples, the proportions of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT‐qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65–0.90), immature B cells (0.76–0.92), and endothelial cells (0.79–0.87), while showing negative correlations with myeloid‐derived suppressor cells (negative 0.54–0.73), T follicular helper cells (negative 0.71–0.86), and natural killer T cells (negative 0.75–0.85).Conclusion: Neutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.

Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30–150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold’s ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold’s capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo’s regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.

Long non‑coding (lnc)RNA KCNQ1 opposite strand/antisense transcript 1 (Kcnq1ot1) has been shown to regulate multiple biological processes. However, the functional role of Kcnq1ot1 in osteoporosis and the underlying mechanism are still unclear. The present study aimed to investigate the function of lncRNA Kcnq1ot1 in osteogenic differentiation. Alkaline phosphatase (ALP) activity was measured using an ALP assay kit. Western blotting was performed to assess the expression levels of osteogenic differentiation‑associated proteins. Reverse transcription‑quantitative PCR was performed to detect Kcnq1ot1, microRNA (miR)‑98‑5p and T‑box transcription factor 5 (Tbx5) expression levels. The binding of Kcnq1ot1 with miR‑98‑5p and that of miR‑98‑5p with Tbx5 were predicted by starBase and TargetScan databases, respectively, and verified using dual luciferase reporter assays. The mineralization of MC3T3‑E1 cells was observed using an Alizarin red S staining assay. The results revealed that expression of Kcnq1ot1 was increased and that of miR‑98‑5p was decreased during osteogenic differentiation. Additionally, Kcnq1ot1 was shown to target miR‑98‑5p and inhibit its expression. Inhibiting miR‑98‑5p reversed the inhibitory effect of Kcnq1ot1 knockdown on osteogenic differentiation and mineralization of MC3T3‑E1 cells. Furthermore, Kcnq1ot1 regulated Tbx5 expression via miR‑98‑5p. Overexpressing miR‑98‑5p or downregulating Tbx5 expression reversed the promotive effect of Kcnq1ot1 overexpression on osteogenic differentiation and mineralization of MC3T3‑E1 cells. In conclusion, these findings suggested that Kcnq1ot1 may promote bone formation by inhibiting miR‑98‑5p and upregulating Tbx5. Kcnq1ot1, miR‑98‑5p and Tbx5 may therefore serve as promising targets for the treatment of osteoporosis.