Diagnosis of periprosthesis joint infection and selection of replantation timing: A novel nomogram diagnosis model.

Preoperative diagnosis of periprosthetic joint infection (PJI) is critical to guide treatment options and improve patient outcomes. In this letter, we discuss results from our experiences with a novel nomogram diagnosis model based on serum and synovial fluid indicators for the preoperative diagnosis of PJI. The results showed that the novel nomogram diagnosis model can distinguish PJI from aseptic loosening before the operation. And it is also a useful candidate for the selection of the timing of current secondary revision.

Multiview representation learning for identification of novel cancer genes and their causative biological mechanisms.

Tumorigenesis arises from the dysfunction of cancer genes, leading to uncontrolled cell proliferation through various mechanisms. Establishing a complete cancer gene catalogue will make precision oncology possible. Although existing methods based on graph neural networks (GNN) are effective in identifying cancer genes, they fall short in effectively integrating data from multiple views and interpreting predictive outcomes. To address these shortcomings, an interpretable representation learning framework IMVRL-GCN is proposed to capture both shared and specific representations from multiview data, offering significant insights into the identification of cancer genes. Experimental results demonstrate that IMVRL-GCN outperforms state-of-the-art cancer gene identification methods and several baselines. Furthermore, IMVRL-GCN is employed to identify a total of 74 high-confidence novel cancer genes, and multiview data analysis highlights the pivotal roles of shared, mutation-specific, and structure-specific representations in discriminating distinctive cancer genes. Exploration of the mechanisms behind their discriminative capabilities suggests that shared representations are strongly associated with gene functions, while mutation-specific and structure-specific representations are linked to mutagenic propensity and functional synergy, respectively. Finally, our in-depth analyses of these candidates suggest potential insights for individualized treatments: afatinib could counteract many mutation-driven risks, and targeting interactions with cancer gene SRC is a reasonable strategy to mitigate interaction-induced risks for NR3C1, RXRA, HNF4A, and SP1.

Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib.

Chemotherapy remains the main approach conserving vision during the treatment of retinoblastoma, the most prevalent eye cancer in children. Unfortunately, the development of chemoresistance stands as the primary reason for treatment failure. Within this study, we showed that prolonged exposure to vincristine led to heightened expression of JAK1 and JAK2 in retinoblastoma cells, while the other members of the JAK family exhibited no such changes. Employing a genetic intervention, we demonstrated the efficacy of depleting either JAK1 or JAK2 in countering vincristine-resistant retinoblastoma cells. In addition, the dual depletion of both JAK1 and JAK2 produced a more potent inhibitory outcome compared to the depletion of either gene alone. We further demonstrated that ruxolitinib, a small molecular inhibitor of JAK1/2, effectively reduced viability and colony formation in vincristine-resistant retinoblastoma cells. It also acts synergistically with vincristine in retinoblastoma cells regardless of inherent cellular and genetic heterogeneity. The effectiveness of ruxolitinib as standalone treatment against chemoresistant retinoblastoma, as well as its combination with vincristine, was validated in multiple retinoblastoma mouse models. Importantly, mice exhibited favorable tolerance to ruxolitinib administration. We confirmed that the underlying mechanism of ruxolitinib's action in chemoresistant retinoblastoma cells is the inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Our study reveals that the underlying mechanism driving ruxolitinib's impact on chemoresistant retinoblastoma cells is the inhibition of JAK/STAT signaling. This study reveals the contribution of JAK1/2 to the development of chemoresistance in retinoblastoma and underscores the effectiveness of targeting JAK1/2 as a strategy to sensitize retinoblastoma to chemotherapy.

Diagnostic and Predictive Efficacy of Synovial Fluid Versus Serum C-Reactive Protein Levels for Periprosthetic Joint Infection and Reimplantation Success.

BACKGROUND: A 2-stage exchange revision for periprosthetic joint infection (PJI) is associated with major risks for reinfection. Although serum markers are frequently used for diagnosis, their effectiveness remains debatable. Synovial fluid markers may offer a more accurate diagnosis of PJI; however, the importance of these biomarkers, notably synovial fluid C-reactive protein (syCRP), remains controversial, particularly in the context of reimplantation. The present study aimed to clarify these diagnostic uncertainties by evaluating the diagnostic efficacy of syCRP versus serum CRP (seCRP) levels in the context of PJI and recurring or persisting infections before reimplantation. METHODS: A total of 186 patients were enrolled and divided into 2 groups: aseptic revision (n = 112) and PJI revision (n = 74). Of the PJI group, 65 were categorized as success and 9 as failure, based on the presence of recurrent or persistent infection before reimplantation. The syCRP and seCRP levels and their changes were assessed preoperatively and in the first-stage and second-stage revisions. Additionally, receiver operating characteristic (ROC) curves and area under the ROC curves (AUCs) were analyzed. RESULTS: Both seCRP and syCRP levels were significantly elevated in the PJI group compared with the aseptic group (P < .001). The ROC curve analysis highlighted the enhanced diagnostic accuracy of syCRP for PJI, with an AUC of 0.93 versus 0.80 for seCRP. Furthermore, syCRP proved to be more reliable in predicting reimplantation success, exhibiting an AUC of 0.86 versus 0.63 for seCRP. In evaluating trends in CRP levels to determine reimplantation timing, changes in syCRP levels demonstrated superior diagnostic utility, exhibiting an AUC of 0.79 versus 0.63 for changes in seCRP levels. CONCLUSIONS: In assessing PJI and infections before reimplantation, syCRP may offer enhanced accuracy compared with seCRP. Nevertheless, variations in both syCRP and seCRP levels did not consistently predict the outcome of reimplantation.

Overexpression of Homeobox A1 Relieves Ovalbumin-Induced Asthma in Mice and Is Associated with Blocking of the NF-κB Signaling Pathway.

Homeobox A1 (HOXA1) is a protein coding gene involved in regulating immunity signaling. This study aims to explore the function and mechanism of HOXA1 in asthma. An asthma mouse model was established via ovalbumin (OVA) induction. Airway hyperresponsiveness was evaluated by the value of pause enhancement (Penh). Inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected by Trypan blue and Wright staining. The pathological morphology of lung tissues was assessed by H&E staining. The IgE and inflammatory biomarkers (IL-1ß, IL-6, IL-17, and TNF-α) in BALF and lung tissues were measured by ELISA. Western blot was performed to detect the expression of NF-κB pathway-related proteins. HOXA1 was down-regulated in OVA-induced asthmatic mice. Overexpression of HOXA1 decreased Penh and relieved pathological injury of lung tissues in OVA-induced mice. Overexpression of HOXA1 also reduced the numbers of total cells, leukocytes, eosinophils, neutrophils, macrophages, and lymphocytes, as well as the levels of IgE, IL-1ß, IL-6, IL-17, and TNF-α in BALF of OVA-induced mice. The inflammatory biomarkers were also decreased in lung tissues by HOXA1 overexpression. In addition, HOXA1 overexpression blocked the NF-κB signaling pathway in OVA-induced mice. Overexpression of HOXA1 relieved OVA-induced asthma in female mice, which is associated with the blocking of the NF-κB signaling pathway.

KIF20B Correlates with LUAD Progression and Is an Independent Risk Factor.

OBJECTIVE: Kinesin family proteins (KIFs) play crucial roles in human tumorigenesis and progression. This study aimed to investigate the expression and association of Kinesin family member 20B (KIF20B) with lung adenocarcinoma (LUAD). METHODS: RNA-seq data from LUAD patients (n = 535) were extracted from TCGA. KIF20B expression was compared between tumor tissues and controls, and between different stages of the disease. Survival and Cox regression analyses were performed, as well as in vitro cellular experiments on A549 cells. RESULTS: KIF20B is upregulated in LUAD tumor tissues compared with controls and is higher in advanced stages. Patients with high expression of KIF20B have shorter survival times. KIF20B is an independent risk factor for the prognosis of LUAD. High KIF20B expression samples were enriched in signaling pathways related to tumor progression. si-KIF20B transfection reduced migration and invasion of A549 cells and increased apoptosis. The expression of p53 and Bax proteins was upregulated by si-KIF20B, while Bcl-2 was down-regulated. DISCUSSION: This study reveals that high KIF20B expression is an independent risk factor for the poor prognosis of LUAD. The inhibition of KIF20B might be of great value for suppressing LUAD progression.

Erratum: SPOP targets oncogenic protein ZBTB3 for destruction to suppress endometrial cancer.

[This corrects the article on p. 2797 in vol. 9, PMID: 31911863.].

Evaluation and Application of Silk Fibroin Based Biomaterials to Promote Cartilage Regeneration in Osteoarthritis Therapy.

Osteoarthritis (OA) is a common joint disease characterized by cartilage damage and degeneration. Traditional treatments such as NSAIDs and joint replacement surgery only relieve pain and do not achieve complete cartilage regeneration. Silk fibroin (SF) biomaterials are novel materials that have been widely studied and applied to cartilage regeneration. By mimicking the fibrous structure and biological activity of collagen, SF biomaterials can promote the proliferation and differentiation of chondrocytes and contribute to the formation of new cartilage tissue. In addition, SF biomaterials have good biocompatibility and biodegradability and can be gradually absorbed and metabolized by the human body. Studies in recent years have shown that SF biomaterials have great potential in treating OA and show good clinical efficacy. Therefore, SF biomaterials are expected to be an effective treatment option for promoting cartilage regeneration and repair in patients with OA. This article provides an overview of the biological characteristics of SF, its role in bone and cartilage injuries, and its prospects in clinical applications to provide new perspectives and references for the field of bone and cartilage repair.

Joint fluid interleukin-6 combined with the neutral polymorphonuclear leukocyte ratio (PMN%) as a diagnostic index for chronic periprosthesis infection after arthroplasty.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice. Many novel serum and joint fluid biomarkers have important implications for the diagnosis of PJI. The presented study evaluated the value of joint fluid interleukin-6 (IL-6) combined with the neutral polymorphonuclear leukocyte (PMN%) ratio for chronic PJI diagnosis after arthroplasty. MATERIALS AND METHODS: Sixty patients with chronic PJI or aseptic failure who underwent hip or knee revision from January 2018 to January 2020 in our department were included in this retrospective study. According to the 2013 MSIS diagnostic criteria, the 60 patients were divided into a PJI group and a non-PJI group (30 patients per group). We collected the joint fluid before surgery and determined the level of IL-6 and the PMN% by ELISA, and the differences between the two groups were compared. The diagnostic efficacy of joint fluid IL-6 combined with PMN% in chronic PJI was analyzed using a receiver operating characteristic curve (ROC curve). RESULTS: The diagnosis of PJI using joint fluid IL-6 combined with PMN% presented an area under the curve of 0.983, which was more accurate than the areas under the curve for diagnosis using IL-6 and PMN% individually (0.901 and 0.914, respectively). The optimal threshold values for IL-6 and PMN% were 662.50 pg/ml and 51.09%, respectively. Their sensitivity and specificity were 96.67% and 93.33%, respectively. The accuracy of the diagnosis of PJI was 95.00%. CONCLUSIONS: Joint fluid IL-6 combined with PMN% can be used as an auxiliary method to detect chronic infection around the prosthesis after hip/knee arthroplasty. LEVEL OF EVIDENCE: Patients who underwent hip/knee revision at the First Hospital of Chongqing Medical University for periprosthetic infection or aseptic failure of the prosthesis after hip/knee arthroplasty from January 2018 to January 2020 were included. Trial registration This study was approved by the ethics committee of the First Hospital of Chongqing Medical University on September 26, 2018 (local ethics committee number: 20187101) and registered with the China Clinical Trials Registry (registration number: ChiCTR1800020440) with an approval date of December 29, 2018.

A decellularized lung extracellular matrix/chondroitin sulfate/gelatin/chitosan-based 3D culture system shapes breast cancer lung metastasis.

Distal metastasis of breast cancer is a primary cause of death, and the lung is a common metastatic target of breast cancer. However, the role of the lung niche in promoting breast cancer progression is not well understood. Engineered three-dimensional (3D) in vitro models capable of bridging this knowledge gap can be specifically designed to mimic crucial characteristics of the lung niche in a more physiologically relevant context than conventional two-dimensional systems. In this study, two 3D culture systems were developed to mimic the late stage of breast cancer progression at a lung metastatic site. These 3D models were created based on a novel decellularized lung extracellular matrix/chondroitin sulfate/gelatin/chitosan composite material and on a porcine decellularized lung matrix (PDLM), with the former tailored with comparable properties (stiffness, pore size, biochemical composition, and microstructure) to that of the in vivo lung matrix. The different microstructure and stiffness of the two types of scaffolds yielded diverse presentations of MCF-7 cells in terms of cell distribution, cell morphology, and migration. Cells showed better extensions with apparent pseudopods and more homogeneous and reduced migration activity on the composite scaffold compared to those on the PDLM scaffold. Furthermore, alveolar-like structures with superior porous connectivity in the composite scaffold remarkably promoted aggressive cell proliferation and viability. In conclusion, a novel lung matrix-mimetic 3D in vitro breast cancer lung metastasis model was developed to clarify the underlying correlativity between lung ECM and breast cancer cells after lung colonization. A better understanding of the effects of biochemical and biophysical environments of the lung matrix on cell behaviors can help elucidate the potential mechanisms of breast cancer progression and further improve target discovery of therapeutic strategies.

Detection of inguinal lymph nodes is promising for the diagnosis of periprosthetic joint infection.

Background: Localized inguinal lymphadenopathy often represents lower extremity pathogen infection, while normalized lymphadenopathy is associated with infection regression. We hypothesized that inguinal lymph nodes (LNs) were enlarged in Periprosthetic Joint Infection (PJI) patients and that normalized inguinal LNs would be a promising way to determine the timing of reimplantation. Methods: We prospectively enrolled 176 patients undergoing primary and revision hip or knee arthroplasty. All patients underwent ultrasound examination of inguinal LNs preoperatively. The diagnostic value of inguinal LNs in PJI was evaluated by the receiver operating characteristic (ROC) curve. Results: The median level of inguinal LNs was 26mm in the revision for PJI group compared with 12 mm in the aseptic revision group (p< 0.0001). The size of the inguinal LNs well distinguishes PJI from aseptic failure (AUC= 0.978) compare with ESR (AUC= 0.707) and CRP (AUC= 0.760). A size of 19mm was determined as the optimal threshold value of the inguinal LNs for the diagnosis of PJI, with a sensitivity of 92% and specificity of 96%. Conclusion: Ultrasonic analysis of inguinal LNs is a valuable piece of evidence for the diagnosis of PJI and evaluation of persistent infection.

lncRNASNP v3: an updated database for functional variants in long non-coding RNAs.

Long non-coding RNAs (lncRNAs) act as versatile regulators of many biological processes and play vital roles in various diseases. lncRNASNP is dedicated to providing a comprehensive repository of single nucleotide polymorphisms (SNPs) and somatic mutations in lncRNAs and their impacts on lncRNA structure and function. Since the last release in 2018, there has been a huge increase in the number of variants and lncRNAs. Thus, we updated the lncRNASNP to version 3 by expanding the species to eight eukaryotic species (human, chimpanzee, pig, mouse, rat, chicken, zebrafish, and fruitfly), updating the data and adding several new features. SNPs in lncRNASNP have increased from 11 181 387 to 67 513 785. The human mutations have increased from 1 174 768 to 2 387 685, including 1 031 639 TCGA mutations and 1 356 046 CosmicNCVs. Compared with the last release, updated and new features in lncRNASNP v3 include (i) SNPs in lncRNAs and their impacts on lncRNAs for eight species, (ii) SNP effects on miRNA-lncRNA interactions for eight species, (iii) lncRNA expression profiles for six species, (iv) disease & GWAS-associated lncRNAs and variants, (v) experimental & predicted lncRNAs and drug target associations and (vi) SNP effects on lncRNA expression (eQTL) across tumor & normal tissues. The lncRNASNP v3 is freely available at http://gong_lab.hzau.edu.cn/lncRNASNP3/.

Systematic analysis of the effects of genetic variants on chromatin accessibility to decipher functional variants in non-coding regions.

Genome-wide association study (GWAS) has identified thousands of single nucleotide polymorphisms (SNPs) associated with complex diseases and traits. However, deciphering the functions of these SNPs still faces challenges. Recent studies have shown that SNPs could alter chromatin accessibility and result in differences in tumor susceptibility between individuals. Therefore, systematically analyzing the effects of SNPs on chromatin accessibility could help decipher the functions of SNPs, especially those in non-coding regions. Using data from The Cancer Genome Atlas (TCGA), chromatin accessibility quantitative trait locus (caQTL) analysis was conducted to estimate the associations between genetic variants and chromatin accessibility. We analyzed caQTLs in 23 human cancer types and identified 9,478 caQTLs in breast carcinoma (BRCA). In BRCA, these caQTLs tend to alter the binding affinity of transcription factors, and open chromatin regions regulated by these caQTLs are enriched in regulatory elements. By integrating with eQTL data, we identified 141 caQTLs showing a strong signal for colocalization with eQTLs. We also identified 173 caQTLs in genome-wide association studies (GWAS) loci and inferred several possible target genes of these caQTLs. By performing survival analysis, we found that ~10% caQTLs potentially influence the prognosis of patients. To facilitate access to relevant data, we developed a user-friendly data portal, BCaQTL (http://gong_lab.hzau.edu.cn/caqtl_database), for data searching and downloading. Our work may facilitate fine-map regulatory mechanisms underlying risk loci of cancer and discover the biomarkers or therapeutic targets for cancer prognosis. The BCaQTL database will be an important resource for genetic and epigenetic studies.

HIF1α Promotes BMP9-Mediated Osteoblastic Differentiation and Vascularization by Interacting with CBFA1.

Bone morphogenetic protein 9 (BMP9) as the most potent osteogenic molecule which initiates the differentiation of stem cells into the osteoblast lineage and regulates angiogenesis, remains unclear how BMP9-regulated angiogenic signaling is coupled to the osteogenic pathway. Hypoxia-inducible factor 1α (HIF1α) is critical for vascularization and osteogenic differentiation and the CBFA1, known as runt-related transcription factor 2 (Runx2) which plays a regulatory role in osteogenesis. This study investigated the combined effect of HIF1α and Runx2 on BMP9-induced osteogenic and angiogenic differentiation of the immortalized mouse embryonic fibroblasts (iMEFs). The effect of HIF1α and Runx2 on the osteogenic and angiogenic differentiation of iMEFs was evaluated. The relationship between HIF1α- and Runx2-mediated angiogenesis during BMP9-regulated osteogenic differentiation of iMEFs was evaluated by ChIP assays. We demonstrated that exogenous expression of HIF1α and Runx2 is coupled to potentiate BMP9-induced osteogenic and angiogenic differentiation both in vitro and animal model. Chromatin immunoprecipitation assays (ChIP) showed that Runx2 is a downstream target of HIF1α that regulates BMP9-mediated osteogenesis and angiogenic differentiation. Our findings reveal that HIF1α immediately regulates Runx2 and may originate an essential regulatory thread to harmonize osteogenic and angiogenic differentiation in iMEFs, and this coupling between HIF1α and Runx2 is essential for bone healing.

Changes in Thromboelastography to Predict Ecchymosis After Knee Arthroplasty: A Promising Guide for the Use of Anticoagulants.

Background: Ecchymosis is one of the worrisome complications after total knee arthroplasty (TKA) and interferes with functional rehabilitation. Current clinical guidelines do not provide individualized approaches for patients with ecchymoses. Methods: In this study, we used thromboelastography (TEG) to determine the coagulation state after TKA and to then explore markers that predict the occurrence of ecchymosis events after TKA. In our cohort, patients were divided into ecchymosis (n = 55) and non-ecchymosis (n = 137) groups according to whether ecchymosis events occurred after TKA. Rivaroxaban 10 mg/d was taken orally for thromboprophylaxis after surgery. All patients completed TEG testing. Correlation analysis was used to determine the risk factors for ecchymosis after TKA, and receiver operating characteristic (ROC) curves for variables with significant correlation were plotted. Results: In all, 55 of the 192 patients (28.65%) developed ecchymosis surrounding the surgical site. Multivariate analysis showed that hidden blood loss (OR = 1.003 and p = 0.005) and changes in the coagulation index (ΔCI) values (OR = 0.351 and p = 0.001) were risk factors for ecchymosis after TKA. Using the Youden index, 0.1805 was determined as the optimal threshold value of ΔCI for predicting the occurrence of ecchymosis, with a sensitivity of 74.55% and specificity of 72.99%. ΔCI is a promising marker as an alarm for the occurrence of ecchymosis after TKA. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800017245). Registered name: The role of thrombelastography in monitoring the changes of coagulation function during perioperative period of arthroplasty. Registered 19 July 2018. http://www.chictr.org.cn/showproj.aspx?proj=29220.

Bone morphogenetic protein 9 enhances osteogenic and angiogenic responses of human amniotic mesenchymal stem cells cocultured with umbilical vein endothelial cells through the PI3K/AKT/m-TOR signaling pathway.

BACKGROUND: Neovascularization plays an essential part in bone fracture and defect healing, constructing tissue engineered bone that targets bone regeneration. Bone morphogenetic protein 9 (BMP9) is a regular indicator that potentiates osteogenic and angiogenic differentiation of MSCs. OBJECTIVES: To investigate the effects of BMP9 on osteogenesis and angiogenesis of human amniotic mesenchymal stem cells (hAMSCs) cocultured with human umbilical vein endothelial cells (HUVECs) and determine the possible underlying molecular mechanism. RESULTS: The isolated hAMSCs expressed surface markers of MSCs. hAMSCs cocultured with HUVECs enhance osteogenic differentiation and upregulate the expression of angiogenic factors. BMP9 not only potentiates angiogenic signaling of hAMSCs cocultured with HUVECs also increases ectopic bone formation and subcutaneous vessel invasion. Mechanically, the coupling effect between osteogenesis and angiogenesis induced by BMP9 was activated by the BMP/Smad and PI3K/AKT/m-TOR signaling pathways. CONCLUSIONS: BMP9-enhanced osteoblastic and angiogenic differentiation in cocultivation with hAMSCs and HUVECs in vitro and in vivo also provide a chance to harness the BMP9-regulated coordinated effect between osteogenic and angiogenic pathways through BMP/Smad and PI3K/AKT/m-TOR signalings. MATERIALS AND METHODS: The ALP and Alizarin Red S staining assay to determine the effects of osteoblastic differentiation. RT-qPCR and western blot was measured the expression of angiogenesis-related factors. Ectopic bone formation was established and retrieved bony masses were subjected to histochemical staining. The angiogenesis ability and vessel invasion were subsequently determined by immunofluorescence staining. Molecular mechanisms such as the BMP/Smad and PI3K/AKT/m-TOR signaling pathways were detected by ELISA and western blot analysis.

Prostate cancer-associated SPOP mutations lead to genomic instability through disruption of the SPOP-HIPK2 axis.

Speckle-type Poz protein (SPOP), an E3 ubiquitin ligase adaptor, is the most frequently mutated gene in prostate cancer. The SPOP-mutated subtype of prostate cancer shows high genomic instability, but the underlying mechanisms causing this phenotype are still largely unknown. Here, we report that upon DNA damage, SPOP is phosphorylated at Ser119 by the ATM serine/threonine kinase, which potentiates the binding of SPOP to homeodomain-interacting protein kinase 2 (HIPK2), resulting in a nondegradative ubiquitination of HIPK2. This modification subsequently increases the phosphorylation activity of HIPK2 toward HP1γ, and then promotes the dissociation of HP1γ from trimethylated (Lys9) histone H3 (H3K9me3) to initiate DNA damage repair. Moreover, the effect of SPOP on the HIPK2-HP1γ axis is abrogated by prostate cancer-associated SPOP mutations. Our findings provide new insights into the molecular mechanism of SPOP mutations-driven genomic instability in prostate cancer.

Astragalus polysaccharide attenuates LPS-related inflammatory osteolysis by suppressing osteoclastogenesis by reducing the MAPK signalling pathway.

Bacterial products can stimulate inflammatory reaction and activate immune cells to enhance the production of inflammatory cytokines, and finally promote osteoclasts recruitment and activity, leading to bone destruction. Unfortunately, effective preventive and treatment measures for inflammatory osteolysis are limited and usually confuse the orthopedist. Astragalus polysaccharide (APS), the main extractive of Astragali Radix, has been widely used for treating inflammatory diseases. In the current study, in vitro and in vivo experimental results demonstrated that APS notably inhibited osteoclast formation and differentiation dose-dependently. Moreover, we found that APS down-regulated RANKL-related osteoclastogenesis and levels of osteoclast marker genes, such as NFATC1, TRAP, c-FOS and cathepsin K. Further underlying mechanism investigation revealed that APS attenuated activity of MAPK signalling pathways (eg ERK, JNK and p38) and ROS production induced by RANKL. Additionally, APS was also found to suppress LPS-related inflammatory osteolysis by decreasing inflammatory factors' production in vivo. Overall, our findings demonstrate that APS effectively down-regulates inflammatory osteolysis due to osteoclast differentiation and has the potential to become an effective treatment of the disorders associated with osteoclast.

Erratum: SPOP targets oncogenic protein ZBTB3 for destruction to suppress endometrial cancer.

[This corrects the article on p. 2797 in vol. 9, PMID: 31911863.].