Tianwen Ye

Objective: The purpose of this study is to identify hub genes associated with both osteoporosis (OP) and chronic kidney disease (CKD) through bioinformatics analysis, and to explore the potential pathogenetic mechanisms in OP and CKD through these hub genes. Methods: We downloaded the GSE15072 and GSE56815 datasets from the GEO database as training sets, and GSE7158 and GSE70528 for validation. Differential expression genes were selected using the “limma” package, while gene co-expression networks were constructed with “WGCNA.” Functional enrichment analyses were performed using “clusterProfiler.” Hub genes were identified through machine learning techniques, and their diagnostic efficacy was evaluated by ROC curves plotted with the ‘pROC’ package. Immune infiltration was analyzed using CIBERSORT, and pan-cancer relationships were explored to identify associations between hub genes and various tumors. Potential therapeutic agents were investigated using the Drug Signatures Database (DSigDB). Experimental validation was conducted via RT-qPCR using cisplatin-induced chronic kidney disease (CKD) and ovariectomy (OVX)-induced osteoporosis models in C57BL/6J mice. After anesthesia and sacrifice, peripheral blood mononuclear cells (PBMCs) were collected to analyze the expression changes of hub genes. Results: This study identified four hub genes (FAM184A, NFKBIA, RP2, HIRA). All hub genes exhibited excellent diagnostic performance, with FAM184A showing the best performance. Immune infiltration analysis revealed the relationships between hub gene expression levels and various immune cells. Pan-cancer analysis revealed the expression levels of FAM184A in different tumors, and it showed that high expression of FAM184A in SARC, SKCM, and PAAD is associated with improved prognosis and reduced mortality rates. Finally, RT-qPCR analysis revealed the mRNA expression levels of the hub genes in both OP and CKD. The mRNA expression of all hub genes were downregulated in osteoporosis model mice compared with normal mice, while in CKD mice, the mRNA expression of all hub genes except FAM184A was upregulated. Conclusions: This study identified four hub genes with significant diagnostic efficacy, suggesting they may act as crucial links between osteoporosis and chronic kidney disease. These genes offer promising targets for the treatment of both diseases. The findings of this study provide valuable insights for future research, which could further elucidate the complex pathogenetic mechanisms connecting chronic kidney disease and osteoporosis.

Objective: The study aimed to explore the safety and effectiveness of percutaneous lordoplasty (PLP) in the treatment of severe osteoporotic vertebral compression fracture (OVCF).Methods: Included in this prospective study were patients with single-segment acute severe OVCF who were treated with PLP in our institution from July 2016 to October 2019. Patients' back pain and quality of life were assessed using the visual analog scale (VAS) and SF-36 scores. Lateral X-ray radiography of the spine was performed to measure the vertebral height, vertebral kyphotic angle, and segmental kyphotic angle, and to evaluate the outcome of fracture reduction and kyphotic correction. Intra-and postoperative complications were recorded.Results: Of the 51 included patients, 47 patients were followed up for 12 months. The VAS score decreased from preoperative 7.33 ± 1.92 to postoperative 1.76 ± 0.85 at the 12th month (p < 0.05), and the SF-36 score increased from preoperative 79.50 ± 9.22 to postoperative 136.94 ± 6.39 at the 12th month (p < 0.05). During the 1-year follow-up period, the anterior height of the vertebral body increased significantly from preoperative 10.49 ± 1.93 mm to 19.33 ± 1.86 mm (p < 0.05); the posterior height of the vertebral body increased insignificantly from preoperative 22.23 ± 2.36 mm to 23.05 ± 1.86 mm (p > 0.05); the vertebral kyphotic angle decreased significantly from preoperative 18.33° ± 11.49° to 8.73° ± 1.21° (p < 0.05); and the segmental kyphotic angle decreased significantly from preoperative 24.48° ± 4.64° to 11.70° ± 1.34° (p < 0.05). During the 1-year follow-up period, there was no significant difference in the radiologic parameters, VAS scores, and SF-36 scores, between the 1st day and the 12th month of post-operation (P > 0.05). No nerve damage occurred in any of the cases. Intraoperative cement leakage occurred in six cases, and the fracture of the adjacent vertebral body occurred in one case.Conclusion: PLP can well reduce the risk of fracture and achieve good kyphotic correction and may prove to be a safe, cost-effective and minimally invasive alternative option for the treatment of severe OVCF with kyphotic deformity.

Osteoarthritis (OA) is one of the most frequent chronic joint diseases with the increasing life expectancy. The main characteristics of the disease are loss of articular cartilage, subchondral bone sclerosis and synovium inflammation. Physical measures, drug therapy and surgery are the mainstay of treatments for OA, whereas drug therapies are mainly limited to analgesics, glucocorticoids, hyaluronic acids and some alternative therapies because of single therapeutic target of OA joints. Baicalein, a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been widely used in anti‐inflammatory therapies. Previous studies revealed that baicalein could alleviate cartilage degeneration effectively by acting on articular chondrocytes. However, the mechanisms involved in baicalein‐mediated protection of the OA are not completely understood in consideration of integrality of arthrosis. In this study, we found that intra‐articular injection of baicalein ameliorated subchondral bone remodelling. Further studies showed that baicalein could decrease the number of differentiated osteoblasts by inhibiting pre‐osteoblasts proliferation and promoting pre‐osteoblasts apoptosis. In addition, baicalein impaired angiogenesis of endothelial cells and inhibited proliferation of synovial cells. Taken together, these results implicated that baicalein might be an effective medicine for treating OA by regulating multiple targets.

Tumor necrosis factor-alpha (TNF-α) promotes osteoclasts differentiation to enhance bone resorption and inhibits osteoblasts differentiation to impair bone formation, which plays a central role in the development of postmenopausal osteoporosis (PMOP). Recent studies implicated an important role of circular RNAs (circRNAs) in osteoporosis. The purpose of this study is to investigate whether circRNAs might be implicated in TNF-α-regulated osteoclasts differentiation and osteoblasts differentiation in PMOP. QRT-PCR was applied to detect expression of circRNA-circHmbox1 and miR-1247-5p in TNF-α-induced osteoclasts differentiation. Western blot, TRAP staining, alkaline phosphatase staining, alizarin red S staining, transwell and cell transfection were conducted to confirm that TNF-α inhibited osteoblasts differentiation by exosomal with low circHmbox1 expression from osteoclasts. Bioinformatics analysis and luciferase reporter revealed the mechanisms of the circHmbox1/miR-1247-5p/B cell lymphoma 6 (Bcl6) interaction. In this study, we found that the level of circRNA-circHmbox1 was obviously reduced in TNF-α-induced osteoclast formation in vivo and in vitro. CircHmbox1 could inhibit RANKL-induced osteoclasts differentiation primarily through binding to microRNA-1247-5p. TNF-α decreased osteoblasts differentiation by exosomal with low circHmbox1 expression from osteoclasts. Mechanistic studies showed that microRNA-1247-5p regulated osteoclasts differentiation and osteoblasts differentiation by targeting Bcl6, which was confirmed to play opposite roles in osteoblasts differentiation and osteoclasts differentiation. Our results provide evidence that circHmbox1-targeting miR-1247-5p is involved in the regulation of bone metabolisms by TNF-α in PMOP.