Osteoarthritis (OA) is a type of arthritis that causes joint pain and limited mobility. In recent years, some studies have shown that the pathological process of OA chondrocytes is related to ferroptosis. Our study aims to identify and validate differentially expressed ferroptosis-related genes (DEFRGs) in OA chondrocytes and to investigate the potential molecular mechanisms. RNA-sequencing and microarray datasets were downloaded from Gene Expression Omnibus (GEO) data repository. Differentially expressed genes (DEGs) were screened by four methods: limma-voom, edgeR, DESeq2, and Wilcoxon rank-sum test. Weighted correlation network analysis (WGCNA), protein-protein interactions (PPI), and cytoHubba of Cytoscape were applied to identify hub genes. Clinical OA cartilage specimens were collected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, western blotting (WB), histological staining, transmission electron microscopy (TEM), and transfection. Sankey diagram was used to visualize the relationships between the expression level of SLC3A2 in the damaged area and clinical factors. Based on bioinformatics analysis, clinical factors, and experiment validation, SLC3A2 was identified as a hub gene. It was down-regulated in OA cartilage compared to normal cartilage (p < 0.05). Functional enrichment analysis revealed that SLC3A2 was associated with ferroptosis-related functions. Spearman correlation analysis showed that the expression level of SLC3A2 in the OA cartilage-damaged area was closely related to BMI, obesity grade, and Kellgren-Lawrence grade. Furthermore, in vitro experiments validated that SLC3A2 inhibited ferroptosis and suppressed cartilage degeneration in OA. In summary, we demonstrated that SLC3A2 inhibited ferroptosis and suppressed cartilage degeneration in OA. These findings provide a new idea for the study of the pathogenesis of OA, thus providing new means for the clinical diagnosis and targeted therapy of OA.

TRNA-derived fragments (tRFs) are new noncoding RNAs, and recent studies have shown that tRNAs and tRFs have important functions in cell metabolism via posttranscriptional regulation of gene expression. However, whether tRFs regulate cellular metabolism of the anterior cruciate ligament (ACL) remains elusive. The aim of this study was to investigate the role and action mechanism of tRFs in ACL cell metabolism. A tRF array was used to determine tRF expression profiles in different human ACL cells, and quantitative real-time polymerase chain reaction and fluorescence in situ hybridisation were used to determine TRF365 expression. ACL cells were transfected with a TRF365 mimic or a TRF365 inhibitor to determine whether TRF365 regulates IKBKB expression. A rescue experiment and dual-luciferase reporter assay were conducted to determine whether the 3′-untranslated region (UTR) of IKBKB has a TRF365-binding site. TRF365 was weakly expressed in osteoarthritis (OA) ACL and interleukin-1β-treated ACL cells. IKBKB was highly expressed in OA ACL and interleukin-1β-treated ACL cells; transfection with the TRF365 mimic suppressed IKBKB expression, whereas transfection with the TRF365 inhibitor had the opposite effect. A dual-luciferase reporter assay showed that TRF365 silenced the expression of IKBKB by binding to its 3′-UTR. Thus, TRF365 regulates the metabolism of ACL cells by targeting IKBKB. In summary, TRF365 may provide a new direction for the study of ACL degeneration and on the pathophysiological process of OA.

TRNA‐derived fragments (tRFs) have been reported to have critical regulatory roles in osteoarthritis (OA). Recent studies have suggested that autophagy promotes the homeostasis of the extracellular matrix of chondrocytes in OA. However, the role of tRFs in posttranscriptional gene regulation during autophagy in OA is unknown. Therefore, we explored the role of tRF‐5009A in the posttranscriptional gene regulation of autophagy and cartilage degeneration in OA. Using RNA sequencing, we identified tRF‐5009A, the tRNA^ValCAC‐derived fragment, in OA tissues and explored its expression by quantitative reverse transcription PCR and fluorescence in situ hybridization. We further investigated the relationship between the expression of tRF‐5009A and clinical factors in OA. Chondrocytes were transfected with a tRF‐5009A inhibitor or mimic to determine their functions, including in relation to autophagy and the cartilage phenotype. A rescue experiment and dual‐luciferase reporter assay were conducted to determine whether the 3′‐untranslated region (UTR) of mTOR contains a tRF‐5009A‐binding site. tRF‐5009A was downregulated in the cartilage of OA knees, especially in damaged areas. mTOR was highly expressed in damaged cartilage and negatively correlated with the expression of tRF‐5009A; transfection with a tRF‐5009A inhibitor promoted the expression of mTOR and suppressed autophagy, whereas transfection with a tRF‐5009A mimic had the opposite effect. A dual‐luciferase reporter assay showed that tRF‐5009A silenced the expression of mTOR by binding to its 3′‐UTR. Thus, tRF‐5009A regulates autophagy and cartilage degeneration in OA by targeting mTOR. In summary, these findings provide an additional tool for the clinical diagnosis and novel targeted therapy of OA.

Comparison of different anticoagulants in blood management and complications with tranexamic acid (TXA) in total hip arthroplasty (THA) is unclear. Our aim was to compare the efficacy and safety among receiving nadroparin calcium, enoxaparin sodium or rivaroxaban after TXA in THA. 150 patients undergoing primary unilateral THA were received 15 mg/kg intravenous TXA (IV-TXA) before skin incision, followed by 1 of nadroparin calcium (Group A), enoxaparin sodium (Group B), or rivaroxaban (Group C) randomly during hospitalization. The primary outcome was hidden blood loss (HBL). Other outcomes such as the maximum hemoglobin (Hb) drop, total blood loss (TBL), the volume of drainage, transfusion rate, length of hospital stay (LOS), and complications were also compared. There were no statistically significant differences in HBL, the maximum hemoglobin (Hb) drop, transfusion rate, and complications among 3 groups. LOS was significantly higher for patients in Group B than Group A (P = .026). Neither deep venous thrombosis (DVT) nor pulmonary embolism (PE) occurred in any group. There were no differences in efficacy and safety in patients undergoing THA receiving nadroparin calcium, enoxaparin sodium, or rivaroxaban after anti-fibrinolysis with TXA.

Osteoarthritis (OA) is a prevalent age‐related disease associated with significant pain and disability. Although 5‐methylcytosine (m ⁵ C) modification is implicated in age‐related diseases, its role in OA remains unclear. Here, the regulatory effects and mechanisms of the m ⁵ C‐related proteins NSUN2 and ALYREF on chondrocyte senescence and inflammation during OA progression were investigated. NSUN2 expression and m ⁵ C modification were upregulated in articular chondrocytes from damaged cartilage of surgically induced OA and naturally aged mice, as well as in primary human chondrocyte aging models. NSUN2 was found to promote chondrocyte senescence and NLRP3 inflammasome activation. Messenger RNA (mRNA) m ⁵ C enrichment, RIP sequencing, and transcriptomic sequencing elucidated the mechanism by which NSUN2 regulates inflammation and aging. IP3R3 was identified as a target gene of NSUN2. Rescue experiments showed that NSUN2 induced Ca ²⁺ overload, which was mitigated by 2‐aminoethoxydiphenyl borate (2‐APB) or BAPTA/AM. NSUN2 knockdown or IP3R3 inhibition protected mouse articular cartilage from senescence and NLRP3 inflammasome activation, alleviating OA progression. Mechanistically, NSUN2 cooperated with the m ⁵ C reader ALYREF to stabilize and promote cytoplasmic export of IP3R3 mRNA, increasing IP3R3 expression. Thus, NSUN2 inhibition reduces chondrocyte senescence and cartilage damage via the IP3R3‐Ca ²⁺ axis, may represent a potential therapeutic target for further investigation.