Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common bone and joint disease. There is currently a lack of effective treatment for GIONFH, and the disease progression may lead to total hip arthroplasty (THA). The exact mechanism of GIONFH pathogenesis remains unsettled, and emerging evidence indicates that the overactivation of osteoclasts plays a pivotal role in the occurrence and progression of this condition. Our previous study has shown that cycloastragenol (CAG), a triterpenoid saponin with multiple bioactivities, is a natural osteoclast inhibitor and has a protective effect on bone loss. However, its effect on GIONFH remains unclear. In this study, methylprednisolone (MPS) (20 mg/kg) was administered via gluteal muscle injection to female Sprague–Dawley (SD) rats to induce GIONFH, and different doses of CAG (5 and 15 mg/kg) were dispensed intraperitoneally for intervention. Micro-CT screening and angiography were applied to determine the shaping of necrotic lesions, the loss of trabecular bone, and the change in the local blood supply. The molecular mechanism was established by Real-time qPCR and Western blotting. Hematoxylin and eosin (H&E) staining was performed to identify empty lacunae in the femoral head. CAG treatment shanked the necrotic lesion area, inhibited the trabecular bone loss, and improved the local blood supply in the femoral head. In addition, CAG medication lowered the ratio of Tnfsf11 (encoding RANKL) to Tnfrsf11b (encoding OPG) and the expression of osteoclast-specific genes, including Acp5 and Ctsk. Consistently, CAG treatment exhibited a dose-dependent weakening effect on the expression of osteoclastogenesis and bone resorption-related proteins, including TRAP, CTSK, and MMP9. CAG addition also alleviated the occurrence of empty lacunae in the subchondral region. Our discoveries demonstrate that CAG is a potential option for hip preservation therapy in GIONFH patients. The protective effect of CAG on rats with GIONFH can be translated into clinical use.

Purpose. The aim of this study is to explore pathological mechanisms of bone fragility in type 2 diabetes mellitus (T2DM) patients. Methods. Identifying common genes for T2DM and osteoporosis by taking the intersection is shared by the Comparative Toxicogenomics Database (CTD), DISEASES, and GeneCards databases. The differentially expressed genes (DEGs) and the differentially expressed miRNAs (DEMs) were identified by analyzing the Gene Expression Omnibus (GEO) datasets (GSE35958, GSE43950, and GSE70318). FunRich and miRNet were applied to predict potential upstream transcription factors and downstream target genes of candidate DEMs, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential mechanisms using Metascape. Eventually, a miRNA‐gene network was constructed by Cytoscape software. Results. 271 common targets and 35 common DEGs between T2DM and osteoporosis were screened out in the above databases, and a total of ten DEMs were obtained in the GSE70318. SP1 was predicted to potentially regulate most of the DEMs. Enrichment analysis showed the PI3K‐Akt signaling pathway and AGE‐RAGE signaling pathway in diabetic complications may play an important role in diabetic skeletal fragility. Two genes (NAMPT and IGFBP5) were considered as key genes involving in the development of diabetic osteoporosis. Through the construction of the miRNA‐gene network, most of the hub genes were found to be potentially modulated by miR‐96‐5p and miR‐7‐5p. Conclusion. The study uncovered several important genes, miRNAs, and pathological mechanisms involved in diabetic skeletal fragility, among which the PI3K‐Akt signaling pathway and AGE‐RAGE signaling pathway in diabetic complications may play important roles.

The purpose of this study was to evaluate the outcomes of total hip arthroplasty (THA) following less invasive hip-preserving procedures (LIHPs) and present a critical overview of the literature to aid in better result interpretation. The search time was from the establishment of the database to September 2021, and the outcome indicators were extracted and analyzed by Cochrane Collaboration Review Manager software (RevMan version 5.4). Finally, 10 articles were included in this meta-analysis by searching Chinese databases and English databases. Three of them were published in Chinese, and the remaining studies were published in English. LIHP was further divided into the tantalum rod implantation group and the non-tantalum rod implantation group. The results showed that prior tantalum rod implantation increased the difficulty of conversion to THA, which was reflected mainly in the longer operative time [weighted mean difference (WMD) = 24.50, 95% confidence interval (CI) = 14.09–34.91, P < 0.00001] and greater intraoperative blood loss (WMD = 114.74, 95% CI = 33.52–195.96, P = 0.006), while no significant difference was found between the non-tantalum rod implantation group and the control group. Simultaneously, easier intraoperative fracture [odds ratio (OR) = 5.88, 95% CI = 0.93–37.05, P = 0.06] and stem malalignment (OR = 4.17, 95% CI = 1.18–14.71, P = 0.03) in the LIHP group tended to be observed than in the control THA group. However, there was no significant difference in cup anteversion and inclination angle, ectopic ossification, postoperative Harris Hip Score and survivorship between the LIHP group and the control group. Although LIHP increased the difficulty of the conversion to THA, it does not detrimentally affect the clinical results of subsequent THA in the mid-term follow-up.

Objective: Osteosarcoma (OS) is a rare and complex form of cancer that mostly affects children and adolescents. Pain is a common symptom for patients in OS which causes significant unhappiness and persistent aches. To date, there is minimal knowledge on the mechanisms underlying OS induced pain and few treatment options for patients. Previous genetic studies have demonstrated that the panel of four genes, artemin ( ARTN ), persephin ( PSPN ), glial cell line-derived neurotropic factor ( GDNF ), and neurturin ( NRTN ) are associated with the regulation of pain processing in OS and analgesic responses. Methods: In the present study, by utilising a scRNA-seq OS dataset, we aimed to measure the gene expression levels of four pain related genes, and compare them between the different cell types in human OS tissues and cell lines. Results: Within a complex and diverse range of cell types in OS tissues, including osteoblastic OS cells, carcinoma associated fibroblasts (CAFs), B cells, myeloid cells 1, myeloid cells 2, NK/T cells, plasmocytes, ARTN and NRTN genes had the highest expression in Osteoblastic OS cells, GDNF gene had a peak expression in carcinoma associated fibroblasts, and PSPN gene in endothelial cells. In addition, all four genes showed deferential pattern of expression in 16 OS cell lines. Conclusion: Future studies should investigate the potential to target deferentially expressed pain-related genes in specific cell types of OS for therapeutic benefit to improve the quality of life for patients living with pain caused by OS.