Objective: Observational studies have shown the association between iron status and osteoarthritis (OA). However, due to difficulties of determining sequential temporality, their causal association is still elusive. Based on the summary data of genome-wide association studies (GWASs) of a large-scale population, this study explored the genetic causal association between iron status and OA. Methods: First, we took a series of quality control steps to select eligible instrumental SNPs which were strongly associated with exposure. The genetic causal association between iron status and OA was analyzed using the two-sample Mendelian randomization (MR). Inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were used for analysis. The results were mainly based on IVW (random effects), followed by sensitivity analysis. IVW and MR-Egger were used for heterogeneity testing. MR-Egger was also used for pleiotropy testing. Leave-one-SNP-out analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Maximum likelihood, penalized weighted median, and IVW (fixed effects) were performed to further validate the reliability of results. Results: IVW results showed that transferrin saturation had a positive causal association with knee osteoarthritis (KOA), hip osteoarthritis (HOA) and KOA or HOA (p < 0.05, OR > 1), and there was a negative causal association between transferrin and HOA and KOA or HOA (p < 0.05, OR < 1). The results of heterogeneity test showed that our IVW analysis results were basically free of heterogeneity (p > 0.05). The results of the pleiotropy test showed that there was no pleiotropy in our IVW analysis (p > 0.05). The analysis results of maximum likelihood, penalized weighted median and IVW (fixed effects) were consistent with our IVW results. No genetic causal association was found between serum iron and ferritin and OA. Conclusions: This study provides evidence of the causal association between iron status and OA, which provides novel insights to the genetic research of OA.

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide. However, effective strategies for cartilage repair are lacking, and patients with advanced OA usually need joint replacement. Better comprehending OA pathogenesis may lead to transformative therapeutics. Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior. Specifically, exosome cargos, such as noncoding RNAs (ncRNAs) and proteins, play a crucial role in OA progression by regulating the proliferation, apoptosis, autophagy, and inflammatory response of joint cells, rendering them promising candidates for OA monitoring and treatment. This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA, suggesting new realms to improve OA management.

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

Background: The use of tranexamic acid (TXA) in primary total hip arthroplasty is well documented. However, considering the potential side effects, including deep vein thrombosis and pulmonary embolism, the ideal method of providing TXA to patients undergoing total hip arthroplasty remains controversial. The objective of this trial was to assess the efficacy and safety of intravenous (IV) administration combined with topical administration of TXA regarding postoperative blood loss and transfusion rates in patients treated with primary unilateral total hip arthroplasty. Methods: In this prospective, randomized controlled trial, 150 patients were divided into three groups: the combined group (IV administration of 15 mg/kg of TXA combined with topical administration of 1 g/100 mL of TXA), the single IV group (IV administration of 15 mg/kg of TXA), and the placebo group. The primary outcomes included blood-loss variables (total, intraoperative, and drainage blood loss; changes in hemoglobin, hematocrit, and platelet concentration; and amount of IV transfusion fluid) and transfusion values (frequency of transfusion and number of transfused blood units). The secondary outcomes included the length of the hospital stay, range of hip motion, Harris hip score, and prevalences of deep vein thrombosis and pulmonary embolism. Results: The total blood loss in the combined group (mean and standard deviation, 835.49 ± 343.50 mL) was significantly reduced (p < 0.05) in comparison with that in the single IV group (1002.62 ± 366.85 mL) and placebo group (1221.11 ± 386.25 mL). The combined group also had fewer transfusions in comparison with the single IV and placebo groups (1, 8, and 19, respectively; p < 0.05). There was no difference among the 3 groups with regard to the rates of deep vein thrombosis or pulmonary embolism. Conclusions: Intravenous combined with topical administration of TXA in patients undergoing a primary unilateral total hip arthroplasty significantly reduced postoperative bleeding and the transfusion rate. Studies with more patients and longer follow-up are needed to confirm whether this promising combined strategy is safe with regard to thromboembolic complications. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.