Long-term safety of lanthanum carbonate in the real word: a 19-year disproportionality analysis from the FDA Adverse Event Reporting System.

BACKGROUND: Lanthanum carbonate is widely used to manage serum phosphate and calcium levels in end-stage kidney disease (ESKD) patients, yet comprehensive long-term safety data are lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) to assess the extended safety profile of lanthanum carbonate. RESEARCH DESIGN AND METHODS: We analyzed FAERS data (2004-2022) to study the association between lanthanum carbonate and adverse events (AEs). Using MedDRA v25.0, we identified risk signals through System Organ Classes (SOCs) and Preferred Terms (PTs). Disproportionality analyzes quantified lanthanum carbonate-associated AE signals. RESULTS: Among 3,284 reports, 2,466 were primary suspected AEs linked to lanthanum carbonate. Males reported AEs more frequently than females. Patients aged over 64 represented the majority. Median onset time for lanthanum carbonate-related AEs was 146 days. Gastrointestinal disorders were prevalent. We identified 16 new signals, including stress, abnormal hepatic function, cholelithiasis, bile duct stone, gastric cancer, and adenocarcinoma gastric. Stress was notable, particularly in male patients over 65 and those with lower weight. CONCLUSIONS: This study affirms lanthanum carbonate's long-term safety for reducing elevated blood phosphorus levels. While gastrointestinal disorders were common, attention must focus on emerging AEs, particularly stress, especially in elderly patients.

Chondroitin Polymerizing Factor (CHPF) promotes cell proliferation and tumor growth in human osteosarcoma by inhibiting SKP2's ubiquitination while activating the AKT pathway.

Osteosarcoma is a common malignant tumor occurring in children and young adults. Chondroitin sulfate (CS) participates in cell adhesion, cell division, and the formation of neural networks in the body, the biosynthesis of which requires the participation of glycosyltransferases. CHPF, a glycosyltransferase, plays a role in the extension of CS. Recently, CHPF's biological roles and functional importance in human diseases including malignant tumors have been widely discussed. However, whether CHPF is involved in osteosarcoma development and growth has not been revealed. The present work aimed to investigate the expression levels, functional significance and molecular mechanism of CHPF in osteosarcoma progression. Our results revealed that CHPF is strongly expressed in osteosarcoma tissues and cells. Furthermore, CHPF serves as a tumor promoter in the development and progression of osteosarcoma through enhancing cell proliferation and migration while suppressing apoptosis. Exploration of the mechanism by which CHPF promotes osteosarcoma indicated that CHPF promotes osteosarcoma through counteracting SKP2's ubiquitination and activating the Akt signaling pathway. For the first time, we clarified the roles of CHPF in osteosarcoma, and our results suggested that CHPF might be a novel therapeutic target in the treatment strategies for osteosarcoma.

Cissus quadrangularis L extract-loaded tricalcium phosphate reinforced natural polymer composite for guided bone regeneration.

Natural medicines plants are significant considerable attention as potential therapeutic agents for bone tissue engineering. Cissus quadrangularis L (CQ). is a potent therapeutic plant known for its own osteogenic properties. In this research work, a phytoconstituents-filled composite was produced by incorporating CQ extract with gelatin (Gel) and pectin (Pec) polymers collective through ß- tricalcium phosphate (ß-TCP) bioceramic via a green template method. The effect of CQ-filled composite morphology and chemical structural properties, in vitro cytotoxicity, cell proliferation, and differentiation was investigated. FTIR spectroscopic results indicated the prepared materials' structural confirmation. The CQ extract was the alcoholic -OH merge with the hydroxyl and -NH groups in the range of 3000 cm-1 to 3500 cm-1. Scanning electron microscopy images showed that the ß-TCP ceramic was perfectly embedded in Gel-Pec polymeric matrix, which is important for bone regeneration. In vitro cell culture results indicated that ß-TCP/Gel-Pec/CQ composite provided 92.0% of a favorable substrate for mesenchymal stem cell viability. The gene expression and RT-PCR studies represent the materials with good osteogenic expression, especially the ß-TCP/Gel-Pec/CQ composite is observed at 168.0% and 188.0% for RUNx2 and OCN, respectively. The result of the physicochemical characterizations and cell viability studies suggest that CQ-loaded ß-TCP/Gel-Pec composite can serve as a potential biomaterial for bone tissue repair and regeneration.

PPARγ inhibits small airway remodeling through mediating the polarization homeostasis of alveolar macrophages in COPD.

The role of Peroxisome Proliferator-Activated Receptor-γ (PPARγ) in alveolar macrophages(AMs) polarization homeostasis is closely associated with airway remodeling in COPD, but the definite mechanism remains unclear. In this study, elevated percentage of M1-type AMs and the expression of functionally cytokines were found in COPD patients and mice, which closely related to the disease severity. PPARγ was markedly up-regulated in M2-type AMs and down-regulated in M1-type AMs, and was associated with disease severity in COPD. Co-cultured with M1- or M2-type AMs promoted the epithelial-mesenchymal transition (EMT) of airway epithelial cells and the proliferation of airway smooth muscle cells. Moreover, airway remodeling and functional damage were observed in both IL4R-/- COPD mice with runaway M1-type AMs polarization and TLR4-/- COPD mice with runaway M2-type AMs polarization. Cigarette extract (CS) or lipopolysaccharide (LPS) stimulated PPARγ-/- AMs showed more serious polarization disorder towards M1, as well as CS induced PPARγ-/- COPD mice, which led to more severe airway inflammation, lung function damage, and airway remodeling. Treatment with PPARγ agonist significantly improved the polarization disorder and function activity in CS/LPS stimulated-AMs by inhibiting the JAK-STAT, MAPK and NF-κB pathways, and alleviated the airway inflammation, restored the lung function and suppressed airway remodeling in CS induced-COPD mice. Our research demonstrates that polarization homeostasis of AMs mediated by PPARγ has the protective effect in airway remodeling, and may be a novel therapeutic target for the intervention and treatment of airway remodeling in COPD.

Semi-blind source separation using convolutive transfer function for nonlinear acoustic echo cancellation.

The recently proposed semi-blind source separation (SBSS) method for nonlinear acoustic echo cancellation (NAEC) outperforms adaptive NAEC in attenuating the nonlinear acoustic echo. However, the multiplicative transfer function (MTF) approximation makes it unsuitable for real-time applications, especially in highly reverberant environments, and the natural gradient makes it hard to balance well between fast convergence speed and stability. In this paper, two more effective SBSS methods based on auxiliary-function-based independent vector analysis (AuxIVA) and independent low-rank matrix analysis (ILRMA) are proposed. The convolutive transfer function approximation is used instead of the MTF so that a long impulse response can be modeled with a short latency. The optimization schemes used in AuxIVA and ILRMA are carefully regularized according to the constrained demixing matrix of NAEC. The experimental results validate significantly better echo cancellation performances of the proposed methods.

Arthroscopic anterior talofibular ligament repair with Internal Brace and lasso-loop technique for chronic ankle lateral instability.

OBJECTIVE: To introduce the surgical technique and clinical outcomes of arthroscopic anterior talofibular ligament (ATFL) repair using the Internal Brace and lasso-loop technique for chronic ankle lateral instability. METHODS: A retrospective study was performed on 29 patients who underwent all-arthroscopic ATFL repair with the Internal Brace and lasso-loop technique from January to August 2020. The patients included 24 males and five females, with a mean age of 30.17 years. Through the accessory anterolateral (AAL) portal, we drilled the bone tunnels and fixed the tape with 4.75 mm and 3.5 mm "SwiveLock" anchors and reattached the torn ligament by the lasso-loop technique. RESULTS: All 29 patients underwent all-arthroscopic procedures smoothly without serious complications, such as infection and important nerve or vessel injuries. There were eight cases of lateral malleolar avulsion fractures and ten cases of talus cartilage injury. The visual analog scale (VAS), Karlsson-Peterson, Tegner, and American Orthopedic Foot and Ankle Society (AOFAS) scores were used to evaluate the clinical consequences. All the patients were followed up for 18.66 ± 4.85 months on average. The average pre-operative VAS score was 4.69 ± 1.04, which was significantly higher than the average post-operative VAS score of 1.14 ± 1.56. At the final follow-up appointments, the averages of Karlsson-Peterson, AOFAS, and Tenger scores were 75.83 ± 9.44, 88.31 ± 6.81, and 6.93 ± 1.79, respectively, which was significantly higher than that before the operation. CONCLUSION: This arthroscopic anterior talofibular ligament repair with the Internal Brace and lasso-loop technique achieves satisfactory clinical outcomes with the benefits of high safety and reliability for chronic ankle lateral instability.

Translational therapy from preclinical animal models for muscle degeneration after rotator cuff injury.

Chronic rotator cuff tears are debilitating diseases which significantly affect patients' quality of life and pose substantial financial burden to the society. The intraoperative reparability of injured tendon and postoperative probability of tendon retear are highly associated with the quality of torn muscles, specifically, the severity of muscle atrophy and fatty infiltration. Animal models that reproduce the characteristic muscle pathology after rotator cuff injury have been developed and used to provide insight into the underlying biology and pathophysiology. In this review, we briefly summarize the current information obtained from preclinical animal studies regarding the degenerative change of cuff muscle subsequent to tendon release and/or suprascapular nerve denervation. Importantly, we focus on the potential translational therapeutic targets or agents for the prevention or reversal of muscle atrophy and fatty infiltration. While further studies are warranted to assess the safety and efficacy of novel therapies derived from these preclinical animal research, we believe that their clinical translation for the treatment of rotator cuff disorders is on the horizon. The Translational potential of this article: Novel therapeutic strategies described in this review from preclinical animal studies hold a great translational potential for preventing or reversing rotator cuff muscle pathology, while further assessments on their safety and efficacy are warranted.

Efficient independent vector extraction of dominant source (L).

The complete decomposition performed by blind source separation is computationally demanding and superfluous when only the speech of one specific target speaker is desired. This letter proposes a computationally efficient blind source extraction method based on the fast fixed-point optimization algorithm under the mild assumption that the average power of the source of interest outweighs the interfering sources. Moreover, a one-unit scaling operation is designed to solve the scaling ambiguity for source extraction. Experiments validate the efficacy of the proposed method in extracting the dominant source.

The miR-302c/transforming growth factor-ß receptor type-2 axis modulates interleukin-1ß-induced degenerative changes in osteoarthritic chondrocytes.

Chondrocyte production of catabolic and inflammatory mediators participating in extracellular matrix degradation has been regarded as a central event in osteoarthritis (OA) development. During OA pathogenesis, interleukin-1ß (IL-1ß) decreases the mRNA expression and protein levels of transforming growth factor-ß receptor type-2 (TGFBR2), thus disrupting transforming growth factor-ß signaling and promoting OA development. In the present study, we attempted to identify the differentially expressed genes in OA chondrocytes upon IL-1ß treatment, investigate their specific roles in OA development, and reveal the underlying mechanism. As shown by online data analysis and experimental results, TGFBR2 expression was significantly downregulated in IL-1ß-treated human primary OA chondrocytes. IL-1ß treatment induced degenerative changes in OA chondrocytes, as manifested by increased matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 proteins, decreased Aggrecan and Collagen II proteins, and suppressed OA chondrocyte proliferation. These degenerative changes were significantly reversed by TGFBR2 overexpression. miR-302c expression was markedly induced by IL-1ß treatment in OA chondrocytes. miR-302c suppressed the expression of TGFBR2 via direct binding to its 3'- untranslated region. Similar to TGFBR2 overexpression, miR-302c inhibition significantly improved IL-1ß-induced degenerative changes in OA chondrocytes. Conversely, TGFBR2 silencing enhanced IL-1ß-induced degenerative changes and significantly reversed the effects of miR-302c inhibition in response to IL-1ß treatment. In conclusion, the miR-302c/TGFBR2 axis could modulate IL-1ß-induced degenerative changes in OA chondrocytes and might become a novel target for OA treatment.

The Effect of Bisphosphonates on Fracture Healing Time and Changes in Bone Mass Density: A Meta-Analysis.

Background: Osteoporosis is a common complication of acute fracture, which can lead to fracture delayed union or other complications and resulting in poor fracture healing. Bisphosphate is a common anti-osteoporosis drug, but its application in fracture patients is still controversial because of its inhibitory effect on bone resorption. Method: Studies were acquired from literature databases in accordance with established inclusion criteria. Standard mean difference (SMD) and 95% confidence intervals (Cls) were calculated to evaluate the effectiveness of the bisphosphonates treatment in fracture patients. Data analysis was conducted with the Review Manager 5.4.1 software. Results: A total of 16 studies involving 5022 patients obtained from selected databases were examined. As expected, bisphosphate had no significant effect on fracture healing time, but it could significantly increase BMD and prevent osteoporosis. Meanwhile, bisphosphate can inhibit both bone resorption and bone formation markers, resulting in low bone turnover state. Conclusion: This meta-analysis showed that bisphosphonate have no significant effect on fracture healing time but they do increase the changes in BMD and reduce bone synthesis and resorption markers. Early application of bisphosphonates after injury in the appropriate patient population should be considered.

Relationship between lipid metabolism and Hedgehog signaling pathway.

The Hedgehog (Hh) signaling pathway is highly conserved signaling pathway in cells. Steroids was found to play a vital role in Hh signaling pathway and aberrant Hh signaling was found to lead a series of disease correlate with abnormal lipid metabolism. This paper aimed to elucidate the relationship between lipid metabolism and Hedgehog signaling pathway.

Inducible expression of Wnt7b promotes bone formation in aged mice and enhances fracture healing.

There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested, Wnt ligands themselves have not been fully explored as a potential therapy. Previous work has demonstrated Wnt7b as an endogenous ligand upregulated during osteoblast differentiation, and that Wnt7b overexpression potently stimulates bone accrual in the mouse. The earlier studies however did not address whether Wnt7b could promote bone formation when specifically applied to aged or fractured bones. Here we have developed a doxycycline-inducible strategy where Wnt7b is temporally induced in the bones of aged mice or during fracture healing. We report that forced expression of Wnt7b for 1 month starting at 15 months of age greatly stimulated trabecular and endosteal bone formation, resulting in a marked increase in bone mass. We further tested the effect of Wnt7b on bone healing in a murine closed femur fracture model. Induced expression of Wnt7b at the onset of fracture did not affect the initial cartilage formation but promoted mineralization of the subsequent bone callus. Thus, targeted delivery of Wnt7b to aged bones or fracture sites may be explored as a potential therapy.

Cyclin D1 regulates osteoarthritis chondrocyte apoptosis via WNT3/ß-catenin signalling.

Objective: Cyclin D1 was an important molecular involved in the pathological process of osteoarthritis (OA). The purpose of this study was to identify the effect and potential mechanism of Cyclin D1 for the proliferation and apoptosis of OA chondrocytes. Methods: We used polymerase chain reaction (PCR) method to identify the expression levels of Cyclin D1 and down-stream Wnt/ß-catenin pathway-related genes in OA chondrocytes according to the grade of OA. Small interfering RNA (siRNA) or overexpression of Cyclin D1 were used to identify the role of Cyclin D1 in cell proliferation and apoptosis. Next, we used XAV-939 to inhibit the Wnt/ß-catenin pathway and explore the relevant mechanism. Results: Cyclin D1 was significantly decreased with OA grade (p < .05). After siCyclin D1 transfection, the expression level of WNT3 and nuclear ß-catenin were significantly increased, while Wnt10a and total ß-catenin were not obviously changed. Co-cultured with XAV-939 and siCyclin D1 abolished the effects of siCyclin D1 on proliferation and apoptosis of OA chondrocytes (p < .05). Conclusions: Cyclin D1 regulated chondrocyte proliferation and apoptosis through Wnt3/ß-catenin instead of Wnt10a/ß-catenin signalling pathway.

MicroRNA-19a-3p promotes rheumatoid arthritis fibroblast-like synoviocytes via targeting SOCS3.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease and effective treatment for RA is still lacking. In this study, the regulatory role of miR-19a-3p in RA was investigated. Quantitative polymerase chain reaction analysis of human blood samples showed that the level of miR-19a-3p was significantly lower in the RA patients compared with that in healthy patients (P < 0.05). In RA fibroblast-like synoviocytes (RAFLS), miR-19a-3p and suppressor of cytokine signaling 3 (SOCS3) were also downregulated and upregulated, respectively, compared with those of normal FLS. Transfection of miR-19a-3p mimic in RAFLS inhibited cell proliferation and promoted cell apoptosis. TargetScan identified SOCS3 as a target of miR-19a-3p, which was confirmed by dual-luciferase assay. Western blot indicated that SOCS3 protein level was significantly decreased after miR-19a-3p overexpression. Moreover, SOCS3 silencing through siRNA transfection also enhanced cell proliferation, meanwhile inhibiting RAFLS apoptosis. In addition, SOCS3 overexpression abrogated the effects of miR-19a-3p overexpression on cell proliferation and apoptosis, corroborating that SOCS3 acts as a downstream effector in the miR-19a-3p-mediated function of RAFLS. These findings suggest that miR-19a-3p plays an important role in RA, and the miR-19a-3p/SOCS3 axis may become a potential therapeutic target for RA.

Tranexamic acid plus drain-clamping can reduce blood loss in total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: The efficacy of tranexamic acid (TXA) plus drain-clamping in reducing blood loss after total knee arthroplasty (TKA) is controversial. This meta-analysis aimed to identify whether combined tranexamic acid and drain-clamping was superior to TXA alone, drain clamping alone and control treatments. METHODS: We searched the PubMed, EMBASE, Web of Science and Google databases and the Cochrane Database of Systematic Reviews. Patients prepared for primary TKA and who underwent TXA plus drain-clamping for blood loss were included in this meta-analysis. Outcomes included the need for transfusion, total blood loss, blood loss in drainage, a decrease in hemoglobin and the occurrence of deep venous thrombosis (DVT). Stata 12.0 was used for meta-analysis. RESULTS: Finally, 7 clinical studies with 839 patients were included in this meta-analysis. Compared with the control group, TXA group and drain clamping group treatments, TXA plus drain-clamping could reduce the need for transfusion, total blood loss, blood loss in drainage and the decrease in hemoglobin with statistically significance. CONCLUSIONS: TXA plus drain-clamping is an efficient method for controlling blood loss after TKA, and more studies should focus on the optimal clamping duration.

[Application of pie-crusting the medial collateral ligament release in arthroscopic surgery for posterior horn of medial meniscus in knee joint].

OBJECTIVE: To explore the effectiveness and safety of pie-crusting the medial collateral ligament release (MCL) in treating posterior horn of medial meniscus (PHMM) tear in tight medial tibiofemoral compartment of knee joint.
 Methods: Thirty-two consecutive patients with PHMM tear in tight medial tibiofemoral compartment of knee joint were admitted to our department from January, 2013 to December, 2014. All patients were performed pie-crusting the MCL release at its tibial insertion with 18-gauge intravenous needle. All patients were evaluated by valgus stress test and bilateral valgus stress radiograph at postoperative 1st day, 4th week and 12th week. Visual Analogue Scales (VAS), Lysholm scores, Tegner scores and International Knee Documentation Committee (IKDC) scores were recorded at the 1st, 3th, 6th month follow-up, then follow-up every 6 months.
 Results: The mean follow-up was 28 (24-36) months. All cases were negative in valgus stress test. MCL rupture, femoral fracture, articular cartilage lesion and neurovascular injury were not found at the last follow-up. The median medial joint space width of affected side and unaffected side for valgus stress radiographs were 6.8 mm and 4.3 mm (P<0.05) at the 1st day, 5.5 mm and 4.2 mm (P<0.05) in the 4th week and 4.8 mm and 4.3 mm (P>0.05) at the 12th week, respectively. VAS scores was changed from 4.5±1.5 preoperatively to 1.7±1.0 at the final follow-up (t=16.561, P<0.05). Lysholm scores was changed from 52.3±5.8 preoperatively to 93.2±6.3 at the final follow-up (t=-41.353, P<0.05). Tegner scores was changed from 4.1±1.1 preoperatively to 5.5±0.6 at the final follow-up (t=-18.792, P<0.05). IKDC scores was changed from 54.5±6.2 preoperative to 93.8±4.5 at the final follow-up (t=-38.253, P<0.05).
 Conclusion: Pie-crusting the medial collateral ligament release is a safe, minimal invasive and effective surgical option for posterior horn of medial meniscus tear in tight medial tibiofemoral compartment of knee joint.

[Treatment of patellofemoral instability in adolescent by anatomical double-bundle medial patellofemoral ligament reconstruction with double suture anchor technique].

OBJECTIVE: To explore the clinical outcomes of anatomical double-bundle medial patellofemoral ligament (MPFL) reconstruction with double suture anchor technique in treating patellofemoral instability in adolescent.
 Methods: Twenty-five young people with patellofemoral instability (25 knees) in our department from January 2013 to December 2014 were enrolled for this study. All patients were performed anatomical double-bundle MPFL reconstruction with arthroscopic-assisted suture anchors technique in the patella, and fixed in the femoral socket with absorbable interference screw. All patients are evaluated by different methods, including patient's satisfaction, patellar apprehension test, recurrent subluxation/dislocation, CT assessment of bone tunnel and patellar tilt angle. Lysholm scores, Tegner scores and Kujala scores were recorded at the final follow-up.
 Results: The mean follow-up was 24 (range 20-40) months. All cases were observed in negative patellar apprehension test. Infection, recurrent subluxation/dislocation and patellar fracture were not found at the last follow-up. CT results demonstrated that the tunnel position were good. The patellar tilt angle was decreased from 21.6°±2.3° to 10.5°±1.6° (P<0.05); the Lysholm scores was increased from 51.7±5.3 to 93.8±6.5 (P<0.05). Tegner scores was increased from 4.1±1.1 to 5.5±0.6 (P<0.05). Kujala scores was increased from 53.5±6.4 to 94.6±4.3 (P<0.05).
 Conclusion: Arthroscopic-assisted anatomical double-bundle MPFL reconstruction with the suture anchors technique is a safe, minimal invasive and effective surgical option for treating patellofemoral instability in adolescent.

The current progress in understanding the molecular functions and mechanisms of visfatin in osteoarthritis.

Osteoarthritis, (OA), also known as degenerative arthritis or degenerative joint disease, is the most common form of arthritis, affecting millions of people worldwide. It is a group of mechanical abnormalities involving degradation of the joints and occurs when the protective cartilage (articular cartilage) on the ends of bones such as the knees, hips and fingers abrades over time. It mainly affects the whole joint structure, including the articular cartilage, subchondral bone and synovial tissue. Extensive work has been done in the past decades to investigate the cellular mechanism of this disease. However, to date, it is still poorly understood, and there is no effective treatment. Recently, both in vitro and in vivo studies have confirmed adipokines play critical roles during OA development. Among these, leptin and adiponectin have been well investigated, whereas the effect of the novel adipokine, visfatin, on OA still needs to be revealed. Therefore, in this short review, we will focus on visfatin and summarize the current progress in the research on its role in OA development.

Endothelin­1 induces oncostatin M expression in osteoarthritis osteoblasts by trans­activating the oncostatin M gene promoter via Ets­1.

Oncostatin M (OSM) contributes to cartilage degeneration in osteoarthritis (OA) and was demonstrated to be expressed in OA osteoblasts. Endothelin­1 (ET­1) is implicated in the degradation of OA articular cartilage, and osteoblast proliferation and bone development. In the present study, the effects of ET­1 on OSM expression in human OA osteoblasts were investigated, to the best of our knowledge, for the first time. Primary human OA osteoblasts were treated with ET­1 (1, 5, 10, 20 and 30 nM) for 0.5, 1, 2, 3 and 4 h with or without the selective ETA receptor (ETAR) antagonist, BQ123, ETB receptor antagonist, BQ788 or the phosphatidylinositol 3­kinase (PI3K) inhibitor, BKM120. ET­1 treatment induced OSM mRNA expression, and the intracellular and secreted protein levels of OA osteoblasts in a dose­dependent manner. This effect was suppressed by BQ123 and BKM120, but not BQ788 administration. In combination with electrophoretic mobility shift assays, deletional and mutational analyses on the activity of a human OSM promoter/luciferase reporter demonstrated that ET­1 induced OSM expression in OA osteoblasts by trans­activating the OSM gene promoter through specific binding of Ets­1 to an Ets­1 binding site in the OSM promoter in an ETAR­ and PI3K­dependent manner. Furthermore, ET­1 treatment increased the expression of Ets­1 in a dose­dependent manner, however the knockdown of Ets­1 suppressed the ET1­induced expression of OSM in OA osteoblasts. In conclusion, the present study demonstrated that ET­1 induces the expression of OSM in OA osteoblasts by trans­activating the OSM gene promoter primarily through increasing the expression level of Ets­1 in an ETAR­ and PI3K­dependent manner. The current study suggested novel insights into the mechanistic role of ET­1 in the pathophysiology of OA.