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Objectives: Aseptic loosening (AL) is the most common reason of total hip arthroplasty (THA) failure and revision surgery. Osteolysis, caused by wear particles released from implant surfaces, has a vital role in AL. Although previous studies suggest that wear particles always lead to osteoblast programmed death in the process of AL, the specific mechanism remains incompletely understood and osteoblast ferroptosis maybe a new mechanism of AL. Materials and Methods: CoCrMo nanoparticles (CoNPs) were prepared to investigate the influence of ferroptosis in osteoblasts and calvaria resorption animal models. Periprosthetic osteolytic bone tissue was collected from patients who underwent AL after THA to verify osteoblast ferroptosis. Results: Our study demonstrated that CoNPs induced significant ferroptosis in osteoblasts and particles induced osteolysis (PIO) animal models. Blocking ferroptosis with specific inhibitor Ferrostatin‐1 dramatically reduced particle‐induced ferroptosis in vitro. Moreover, in osteoblasts, CoNPs significantly downregulated the expression of Nrf2 (nuclear factor erythroid 2‐related factor 2), a core element in the antioxidant response. The overexpression of Nrf2 by siKeap1 or Nrf2 activator Oltipraz obviously upregulated antioxidant response elements (AREs) and suppressed ferroptosis in osteoblasts. Furthermore, in PIO animal models, the combined utilization of Ferrostatin‐1 and Oltipraz dramatically ameliorated ferroptosis and the severity of osteolysis. Conclusions: These results indicate that CoNPs promote osteoblast ferroptosis by regulating the Nrf2‐ARE signalling pathway, which suggests a new mechanism underlying PIO and represents a potential therapeutic approach for AL. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the anti-inflammatory effectiveness of celecoxib and its effect on the rehabilitation of joint function after total knee arthroplasty.Methods: 72 patients presented between 2016 and 2017 and were divided into two groups. The experimental group was given 200 mg celecoxib twice daily with tramadol hydrochloride 50 mg twice daily (as required); the control group was given tramadol hydrochloride 50 mg twice daily for 6 weeks from the first day after total knee arthroplasty. Skin temperature around the knee was measured 1 day before surgery, on postoperative days 1 and 3, and at weeks 1, 2, and 6. Inflammatory markers (white blood cell count, C-reactive protein, erythrocyte sedimentation rate, and interleukin-6) were measured preoperatively, on postoperative day 3, and at weeks 1 and 6. Knee Society Score was recorded preoperatively and at postoperative weeks 1, 2, and 6.Results: Except for preoperative skin temperature, the recorded skin temperatures of the experimental group were significantly different compared to those of the control group (p = 0.001, 0.024, 0.030, 0.041, 0.047, respectively). Levels of C-reactive protein were significantly different at the 1st and the 6th week after surgery, differing by 19.3 ± 4.64 mg/L (p < 0.001) and 2.6 ± 0.92 mg/L (p = 0.006). Levels of interleukin-6 showed a significant difference of 6.61 ± 2.36 pg/mL (p = 0.007) at the 1st week after surgery. Until the 6th week after surgery, the erythrocyte sedimentation rate in the experimental group and the control group differed by 17 ± 4.6 mm/h (p = 0.001).Conclusions: Celecoxib has a significant inhibitory effect on postoperative aseptic inflammation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of body mass index (BMI) and hip anatomy on direct anterior approach (DAA) total hip replacement.Subjects and Methods: The study is a retrospective analysis of 124 cases of DAA total hip replacement from 2009 to 2012. The BMI, the ratio of the greater trochanter (GT) and anterior superior iliac spine (ASIS) bilaterally (GT/ASIS), and the vertical distance between the ASIS and GT (AGVD) were obtained from medical records. All cases were categorized into three groups (43, 49, and 32 cases in each group, respectively) based on BMI (BMI <18.5, BMI 18.5-25, and BMI >25) or divided into two groups based on GT/ASIS (≤1.17 or >1.17) or AGVD (≤86 or >86 mm). Operating time, intraoperative bleeding, and surgical complications were compared between different groups.Results: A longer average operating time, more intraoperative bleeding, and a higher rate of complications were observed in the group with the highest BMI. The complications included a case of intraoperative femur fracture, a wound hematoma, and a lateral femoral cutaneous nerve injury. The group with higher GT/ASIS had a shorter average operating time, less bleeding, and a lower complication rate than the group with lower GT/ASIS. Moreover, the group with higher AGVD showed a shorter average operating time, less bleeding, and a lower complication rate compared with the group with lower AGVD.Conclusion: Our study suggests that lower BMI and larger GT/ASIS and AGVD are associated with a shorter operating time, less bleeding, and a lower complication rate in DAA total hip replacement. These findings are valuable for clinicians to make the appropriate choice of surgery types for different individuals. [ABSTRACT FROM AUTHOR]

Collagen triple helix repeat containing-1 (CTHRC1), a secreted protein, is transiently expressed in the arterial wall in response to injury, indicating that it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration. Recent studies showed that it is aberrantly upregulated in most human solid tumors, yet its role in osteosarcoma remains unclear. In this study, the authors investigated the role of CTHRC1 in human osteosarcoma tumorigenesis. The authors used lentivirus-mediated short hairpin RNA (shRNA) against CTHRC1 to limit its endogenous expression in U2OS and SW1353 cells. Interestingly, they found that depletion of CTHRC1 significantly inhibited cell proliferation and colony formation in U2OS and SW1353 cells. Flow cytometry assay showed that knockdown of CTHRC1 increased the cell percentage of G0/G1 phase, resulting in cell cycle arrest in U2OS cells. Moreover, CTHRC1 silencing induced the cell cycle arrest by a decrease in the cell percentage in G0/G1 phase and increased in G2/M phase in SW1353 cells. In addition, crystal violet staining suggested CTHRC1 silencing inhibited migration of U2OS and SW1353 cells. These results demonstrated that CTHRC1 might play an important role in osteosarcoma progression. [ABSTRACT FROM AUTHOR]

Purpose: Suture fixation is mostly used in arthroscopic treatment of tibial eminence avulsion fractures. However, no clinical studies of metal cable fixation have been reported. We hypothesised that cable fixation can provide equal stability and clinical outcome compared with Ethibond sutures. Methods: Between 2007 and 2008, we treated 42 patients of adult type III tibial eminence avulsion fractures. Twenty-three patients were male, and 19 were female. All patients were confirmed by radiographs, MRI, and arthroscopy during surgery. Ligament injury and meniscus tears were excluded from this study. Twenty-two patients were treated with No. 2 Ethibond suture fixation (group I), and 20 were treated with cable fixation under arthroscopy (group II). Follow-up assessments included imaging evaluation, Lysholm knee score, International Knee Documentation Committee (IKDC) classification, and the Lachman test. Results: Bone union was found in radiographic evaluation in all patients within 3 months. At the last follow-up, there was neither extension nor flexion limitation in any patient. There were no significant differences in the Lysholm score between the two groups at follow-up. All 42 patients were classified by the IKDC as normal or nearly normal. Stability based on the Lachman test showed two patients of grade II laxity in group I. At the final follow-up, all 42 patients had returned to their pre-injury activities. Conclusions: Cable fixation to treat type III tibial eminence avulsion fracture can provide a clinical outcome equal to that of Ethibond sutures. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether or not reconstruction of the medial cortex in subtrochanteric fracture can reduce the risks of internal fixation failure, fracture malunion, and nonunion. Subjects and Methods: Between 2005 and 2008, 46 patients with subtrochanteric fracture were treated with intramedullary nailing and followed up. The average age was 42 years. According to the Seinsheimer classification, 26 patients were type IIIA, 7 were type IIIB, 11 were type IV and 2 were type V. Medial cortex alignment was achieved under traction in 40 cases. In 5 cases, the medial fractures were too far away and we used minimally invasive open reduction with wire or titanium cable cerclage. In 1 case of type IIIA subtrochanteric fracture, the displaced medial fracture was not reconstructed and was fixed with a long Gamma nail. We reviewed all patients' radiographs before and after treatment to evaluate bone healing. Results: The 46 patients were followed up for an average of 24.3 months. Bone union was achieved within an average of 18.7 weeks in 45 cases. One case, a type IIIA fracture nonunion with displaced medial fracture, was not reconstructed. Instead, we used a free fibular transplantation on the medial side and fracture union was achieved 6 months after revision surgery. Conclusions: In reconstructing the medial cortex in subtrochanteric fracture treatment, continuity and integrity are important. They can reduce the failure of internal fixation and the incidence of nonunion. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We aimed to identify RNA N6-methyladenosine methylation associated genes in osteoarthritis (OA), and to explore possible regulatory mechanisms of these RNA methylation associated genes. Bioinformatics analyses, including differential expression analysis, functional enrichment analysis, verification analysis, and box plot analysis, were conducted based on different datasets from OA and non-OA patients. Gene expression at mRNA and protein levels was determined by quantitative reverse transcription PCR, western blot and immunofluorescence. Interleukin 1β (IL-1β)-treated SW1353 cells was used as cell model. Lentiviral vector was used for over-expression METTL3 in vitro. CCK-8 assay kit was used to determine cell viability and inflammatory cytokines (IL-1α, IL-6, IL-8, IL-10 and TNF-α) was detected using ELISA kits. Bioinformatics analysis showed that METTL3 expression was decreased in OA group, which was confirmed in clinical samples. Expression of METTL3 was also reduced in IL-1β-treated cells. Levels of inflammatory cytokines were obviously reduced in the METTL3 overexpression group, while IL-1β treatment reversed such decrease caused by METTL3 overexpression (p < 0.05). Both METTL3 overexpression and IL-1β treatment promoted expression of p65 protein and p-ERK (p < 0.01). Additionally, increased expression of MMP1 and MMP3 , and decreased expression of MMP13 , TIMP-1 , and TIMP-2 at both mRNA and protein levels were observed in the METTL3 overexpression group when compared with the control group (p < 0.01). Expression of m6A methylation gene METTL3 was reduced in OA. METTL3 is involved in OA probably by regulating the inflammatory response. METTL 3 overexpression may affect extracellular matrix degradation in OA by adjusting the balance between TIMPs and MMPs. • METTL3 and YTHDC2 were identified as m6A methylation-related genes in OA. • METTL3 may be involved in OA by regulating the inflammatory response. • METTL3 overexpression may affect ECM degradation in OA. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a highly prevalent joint disease; however, effective treatments are lacking. Protopine (PTP) is an isoquinoline alkaloid with potent anti-inflammatory and antioxidant properties; however, it has not been studied in osteoarthritis. This study aimed to investigate whether PTP can effectively protect chondrocytes from ferroptosis. Primary mouse chondrocytes were treated with tert -butyl hydroperoxide (TBHP) to simulate oxidative stress in an in vitro model of osteoarthritis. Two concentrations of PTP (10 and 20 μg/mL) were validated for in vitro experiments. Cellular inflammation and metabolism were detected using RT-qPCR and western blotting (WB). Ferroptosis was assessed via WB, qPCR, reactive oxygen species (ROS) levels, lipid ROS, and immunofluorescence staining. In vitro, PTP significantly ameliorated chondrocyte inflammation and cytolytic metabolism and significantly suppressed chondrocyte ferroptosis through the activation of the Nrf2 pathway. The anterior cruciate ligament transection (ACLT) mouse model was used to validate the in vivo effects of PTP. The joint cartilage was assessed using the Osteoarthritis Research Society International (OARSI) score, Safranin O staining, and immunohistochemistry. The intra-articular administration of PTP alleviated cartilage inflammation and ferroptosis, as evidenced by the expression of MMP3, MMP13, COL2A1, GPX4, and Nrf2. Overall, we find that PTP exerted anti-ferroptosis and anti-inflammatory effects on chondrocytes to protect the articular cartilage. • PTP is an isoquinoline alkaloid with anti-inflammatory and antioxidant properties. • PTP significantly ameliorated chondrocyte inflammation and ferroptosis. • Repression of chondrocyte ferroptosis was mediated by activating the Nrf2 pathway. • PTP exerts these effects on chondrocytes to protect the articular cartilage. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) rapidly spreads worldwide and causes more suffering. The relation about the aggravation of inguinal pain and COVID-19 was unclear in patients with total hip arthroplasty (THA). This study aimed to evaluate the risk of groin pain aggravation in short-term THA patients after COVID-19. Methods: Between 2020 and 2022, 129 patients with THA who were affected COVID-19 were enrolled. A short-standardized questionnaire was administered during follow-up to inquire about the aggravation of groin ache before and after SARS-COV-2 affection. Furthermore, we evaluated the potential association between the presence of increased pain and various factors, including age, gender, body mass index, diagnosis, and length of hospital stay. Results: The case-crossover study revealed an increased risk of inguinal soreness aggravation when comparing 8 weeks after COVID-19 with 12 weeks before COVID-19 (Relative risk [RR], 9.5; 95% Confidence intervals [CI], 2.259–39.954). For COVID-19 positive patients, multivariate analysis showed length of stay was an independent factor significantly associated with increased risk of aggravation of groin pain (Odds ratio [OR], 1.26; 95%CI, 1.03–1.55, p = 0.027). Conclusion: This study confirms the association between COVID-19 and the exacerbation of soreness in the groin region in THA patients and extended length of stay is a possible contributing factor. This study expands the current literature by investigating the risk of aggravation of inguinal pain in patients with THA after COVID-19, providing valuable insights into postoperative outcomes in this specific population. Trial registration This retrospective study was approved by the Institutional Review Board of Shanghai general hospital (No.2023-264). [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disorder that causes cartilage degradation and subchondral bone abnormalities. Nangibotide, also known as LR12, is a dodecapeptide with considerable anti-inflammatory properties, but its significance in OA is uncertain. The aim of the study was to determine whether nangibotide could attenuate the progression of OA, and elucidate the underlying mechanism. In vitro experiments showed that nangibotide strongly inhibited TNF-α-induced osteogenic reduction, significantly enhanced osteoblast proliferation and prevented apoptosis in MC3T3-E1 cells. Male C57BL/6 J mice aged 2 months were randomly allocated to three groups: sham, ACLT, and ACLT with nangibotide therapy. Nangibotide suppressed ACLT-induced cartilage degradation and MMP-13 expression. MicroCT analysis revealed that nangibotide attenuated in vivo subchondral bone loss induced by ACLT. Histomorphometry results showed that nangibotide attenuated ACLT-induced osteoblast inhibition; TUNEL assays and immunohistochemical staining of cleaved-caspase3 further confirmed the in vivo anti-apoptotic effect of nangibotide on osteoblasts. Furthermore, we found that nangibotide exerted protective effects by suppressing TGF-β signaling mediated by Smad2/3 to restore coupled bone remodeling in the subchondral bone. In conclusion, the findings suggest that nangibotide might exert a protective effect on the bone-cartilage unit and maybe an alternative treatment option for OA. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn't been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. Methods: LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. Results: We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. Conclusions: These results showed that TOD can be adopted as a potential therapeutic agent for OA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is generally considered to be characterized by progressive articular cartilage destruction. Increasing evidence demonstrates that CDK9, which is a member of cyclin-dependent kinase family, plays a significant role in the regulation of acute and chronic inflammatory diseases. IL-1β, a major proinflammatory cytokine, was used to establish a model of OA in vitro after stimulating chondrocytes. We found that CDK9 was highly expressed in in vitro and in vivo models of inflammation. The role of LDC000067 (abbreviated as LDC067), a specific inhibitor of CDK9, in protecting articular cartilage from immune response has not been fully clarified. Intriguingly, in this study, we demonstrated that LDC067 prevented IL-1β-induced production of metalloproteinases (MMPs) and inflammatory cytokines, including MMP3, MMP9, MMP13, IL-6, IL-8 and TNF-ɑ. Furthermore, we revealed that LDC067 inhibited IL-1β-induced NF-κB signaling pathway activation in chondrocytes. The inhibition of CDK9 could also delay cartilage degeneration in an anterior cruciate ligament transection (ACLT) mouse model in vivo. Taken together, these results highlighted the significance of this CDK9 inhibitor in preventing cartilage destruction and indicated that LDC067 might serve as a potential therapeutic agent for OA. • CDK9 is upregulated in osteoarthritis cartilage and is correlated with the severity of OA. • The specific inhibitor of CDK9, LDC067 attenuates the catabolism and hypertrophic changes of chondrocytes in vitro. • LDC067 suppresses the activation of the NF-κB signaling pathway. • LDC067 ameliorates OA cartilage destruction in vivo and may be a novel therapeutic agent. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) has traditionally been defined as a non-inflammatory disease. Recently, many studies have demonstrated that OA also has an inflammatory component. BRD4, a member of the Bromodomain and Extra-Terminal Domain family, has emerged as an important regulator of some chronic inflammatory diseases. JQ1, an antagonist of BRD4, modulates transcription of several genes. Our study demonstrated that BRD4 is up-regulated in articular cartilage of OA. BRD4 inhibition attenuated the inflammation and catabolism of chondrocytes and suppressed NF-κB signalling pathway activation. In addition, BRD4 inhibition abolished the transcriptional activity of High Mobility Group Protein B1 (HMGB1). We identified HMGB1 as a direct target of BRD4. Genetic and pharmacological inhibition of BRD4 suppressed IL-1β-induced expression and translocation of HMGB1. Chromatin immunoprecipitation (ChIP) showed the enrichment of BRD4 around the HMGB1 upstream non-promoter region, which diminished with JQ1 treatment. Finally, haematoxylin & eosin and Safranin o/Fast Green staining demonstrated that JQ1 attenuates cartilage destruction in mice with anterior cruciate ligament transection without significant toxic effects. These studies highlighted the importance of BRD4 in the chronic inflammatory reactions of OA, which, as far as we know, was the first report of this finding, and suggested that BRD4 might be a novel potential therapeutic target for the treatment of OA. [ABSTRACT FROM AUTHOR]

[Display omitted] • CoP-challenged macrophages can accelerate osteoclastogenesis. • CoPs result in macrophages pyroptosis and release of inflammatory cytokines. • CoPs stimulation promotes ROS accumulation and subsequently activates NLRP3. • High-concentration CoPs suppress mitophagy, further enhancing macrophages pyroptosis. • By promoting mitophagy and inhibiting NLRP3, CoP-induced osteolysis can be delayed. Wear particles derived from implant surfaces are the important factors causing periprosthetic osteolysis (PPO), which is the main reason for total joint revision. To date, the specific pathogenesis of PPO remains largely unknown, and developing new therapeutic strategies is urgently necessary. Our study indicated the most clinically common cobalt- chromium-molybdenum (CoCrMo) wear particles (CoPs) activated macrophages and further accelerated osteoclastogenesis. Subsequently, we put emphasis on the pathologic change in macrophages after CoPs stimulation. Meaningfully, high-concentration CoPs induced reactive oxygen species (ROS) accumulation in macrophages and activated NOD-like receptor pyrin domain-containing 3 (NLRP3)-dependent pyroptosis, promoting the release of cytokines such as IL-18, IL-1β and HMGB1, and subsequent formation of extracellular inflammatory microenvironment, which is crucial for osteoclastogenesis. More interestingly, transmission electron microscopy and flow cytometry results revealed that there were accumulation of endamaged mitochondria in high-concentration CoP-challenged macrophages, which accelerated intracellular ROS accumulation and mediated NLRP3-dependent pyroptosis. Mechanismly, high-concentration CoPs induced macrophage mitophagy impairment and the loss of mitochondrial membrane potential via inhibiting PINK1/Parkin signalling pathway. Furthermore, by subcutaneous injection of salidroside and/or CY-09 in situ significantly delayed CoP-induced mice calvaria osteolysis. Collectively, this study demonstrates a novel mechanism underlying the pathogenesis of PPO and provides a potential therapy avenue. [ABSTRACT FROM AUTHOR]

• EsA attenuates inflammation and catabolism of chondrocytes. • EsA restrains RANKL-induced osteoclast formation. • Treatment with EsA suppresses NF-κB and MAPK signalling pathway activation in vitro. • EsA protects OA cartilage in vivo and may be a novel therapeutic target. Osteoarthritis is a relatively common disorder of articular deterioration related to cartilage damage, subchondral bone remodelling, inflammation and metabolism. Agents that can inhibit cartilage degradation and osteoclastogenesis are required for the prevention and treatment of osteoarthritis. Esculentoside A, the highest concentration triterpene saponin isolated from the root of Phytolacca esculenta, has commonly been used for the treatment of chronic bronchitis. However, the role esculentoside A plays in ameliorating osteoarthritis has not been reported. We found that esculentoside A suppresses the expression of IL-1β-induced inflammatory and metabolic factors (IL-6, IL-8, TNF-α, MMP2, MMP3 and MMP13). In addition, esculentoside A restrains osteoclast formation by inhibiting the marker gene expression of NFATc1 and c-Fos. Our results indicate that esculentoside A markedly suppresses IL-1β-induced NF-κB and MAPK signalling pathway activation in chondrocytes, and inhibits RANKL-induced osteoclast precursor generation. Finally, treatment with esculentoside A inhibits the progressive cartilage degeneration and osteoclastogenesis in osteoarthritis mouse models. In summary, these results demonstrate that esculentoside A could be a latent therapeutic reagent for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]