The lncRNA MEG3 downregulation leads to osteoarthritis progression via miR-16/SMAD7 axis

Abstract Background Osteoarthritis (OA) is a chronic joint disease and there is no a definitive cure at present. Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in the development of OA. However, the underlying mechanism of lncRNA maternally expressed gene 3 (MEG3) in OA has not been well elucidated. Methods The rat OA model and interleukin-1β (IL-1β)-induced rat chondrocytes were constructed. The expression pattern of lncRNA MEG3 and miR-16 was detected by RT-qPCR assay in cartilage tissues of rat OA model. The effect of MEG3 and miR-16 on IL-1β-induced chondrocytes was evaluated on the basis of cell viability and apoptosis. Then, the interaction among MEG3, miR-16 SMAD7 was explored by dual-luciferase reporter assay and RIP assay. Results It is found that lncRNA MEG3 was down-regulated and miR-16 was up-regulated in rat OA cartilage tissues. MEG3 knockdown promoted proliferation and inhibited apoptosis, while miR-16 knockdown suppressed proliferation and promoted apoptosis in IL-1β-induced rat chondrocytes. Moreover, MEG3 was involved in miR-16 pathway and MEG3 suppressed miR-16 expression. Additionally, SMAD7 was a target gene of miR-16 and miR-16 suppressed SMAD7 expression in IL-1β-induced chondrocytes. Moreover, the expression of SMAD7 induced by MEG3 or si-MEG3 was markedly reversed by the introduction of miR-16 or anti-miR-16. Furthermore, MEG3 exerted its anti-proliferation and pro-apoptosis by regulating miR-16 and SMAD7. Conclusion MEG3 was down-regulated and miR-16 was up-regulated in cartilage tissues of rat OA model. MEG3 knockdown might lead to the progression of OA through miR-16/SMAD7 axis

Cost-Effectiveness Analysis Based on Intelligent Electronic Medical Arthroscopy for the Treatment of Varus Knee Osteoarthritis

The incidence of inverted knee osteoarthritis is slowly increasing, there are technical limitations in the treatment, and the operation is difficult. In this article, we will study the benefits and costs of arthroscopic cleaning treatments based on intelligent electronic medicine. This article focuses on knee osteoarthritis patients in the EL database. There are 12 male patients, accounting for 66.67%, and 6 female patients, accounting for 33.33%. The average body mass index (BMI) of the patients was 28.08, the average time from first knee discomfort to surgery was 28.44 months, and the average time of arthroscopic debridement treatment for patients with VKOH knee osteoarthritis was 143.11 minutes. One case of perioperative complication occurred within 35 days after operation, which was a soleus muscle intermuscular venous thrombosis. After immobilization and enhanced anticoagulation for 1 week, it was stable without risk of shedding. The average postoperative study time was 20.00 months. The electronic medical arthroscopy cleaning treatment plan in this article can greatly improve the quality of life of patients and can check the pathological state in time, with low cost. In the course of treatment, comprehensive treatment costs can be saved by 45%. Arthroscopic clean-up treatment can not only reduce knee pain and other uncomfortable symptoms, restore normal knee joint function, and improve the quality of life of patients, but also correct the unequal length of the lower limbs, thereby avoiding spinal degeneration caused by knee instability. Therefore, it is the first choice for the treatment of advanced knee osteoarthritis in patients with VKOH

Downregulation of lncRNA NEAT1 interacts with miR-374b-5p/PGAP1 axis to aggravate the development of osteoarthritis

Abstract Background Osteoarthritis (OA), characterized by inflammation and articular cartilage degradation, is a prevalent arthritis among geriatric population. This paper was to scrutinize the novel mechanism of long noncoding RNA (lncRNA) NEAT1 in OA etiology. Methods A total of 10 OA patients and 10 normal individuals was included in this study. Cell model of OA was built in human normal chondrocytes induced by lipopolysaccharide (LPS). An OA Wistar rat model was established through intra-articular injection of L-cysteine and papain mixtures (proportion at 1:2) into the right knee. Quantitative reverse transcription-polymerase chain reaction was employed to ascertain the expression levels of NEAT1, microRNA (miR)-374b-5p and post-GPI attachment to protein 1 (PGAP1), while dual-luciferase reporter experiments were used for the validation of target relationship among them. Cell cycle and apoptosis were calculated by flow cytometry analysis. CCK-8 assay was done to evaluate the proliferative potentials of chondrocytes. The levels of cell cycle-related proteins (Cyclin A1, Cyclin B1 and Cyclin D2) and pro-apoptotic proteins (Caspase3 and Caspase9) were measured by western blotting. Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 levels were determined via ELISA. Hematoxylin & eosin (HE) Staining was used for pathological examination in OA rats. Results Pronounced downregulation of NEAT1 and PGAP1 and high amounts of miR-374b-5p were identified in OA patients, LPS-induced chondrocytes and OA rats. NEAT1 targeted miR-374b-5p to control PGAP1 expression. Loss of NEAT1 or upregulation of miR-374b-5p dramatically accelerated apoptosis, led to the G1/S arrest and promoted the secretion of inflammatory cytokines in LPS-induced chondrocytes, while ectopic expression of PGAP1 exhibited the opposite influences on chondrocytes. Additionally, we further indicated that upregulation of miR-374b-5p attenuated the effects of PGAP1 overexpression on LPS-induced chondrocytes. Conclusions Reduced NEAT1 induces the development of OA via miR-374b-5p/PGAP1 pathway. This suggests that the regulatory axis NEAT1/miR-374b-5p/PGAP1 is a novel and prospective target for OA treatment

Data from: Prednisolone induces osteoporosis-like phenotypes via focal adhesion signaling pathway in zebrafish larvae

Patients taking glucocorticoid or glucocorticoid-like drugs for an extended period of time may develop osteoporosis, termed glucocorticoid-induced osteoporosis (GIOP). GIOP is the most common form of secondary osteoporosis, but the mechanism underlying its development is unclear. In the present study, we used prednisolone to treat zebrafish larvae to investigate GIOP. Our RNA deep-sequencing (RNA-seq) results show that prednisolone affects genes known to act in the extracellular region. Therefore the extracellular region, extracellular matrix, and collagen trimer might be involved in glucocorticoid-induced osteoporosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the focal adhesion signaling pathway is the most enriched signaling pathway in terms of differentially expressed genes (DEGs). In this pathway, two adapter proteins, itga10 and itgbl1, were down-regulated in the prednisolone-treated larvae. Further experiments showed that prednisolone contributes to GIOP by down-regulating itga10 and itgbl1

Prednisolone induces osteoporosis-like phenotypes via focal adhesion signaling pathway in zebrafish larvae

Patients taking glucocorticoid or glucocorticoid-like drugs for an extended period of time may develop osteoporosis, termed glucocorticoid-induced osteoporosis (GIOP). GIOP is the most common form of secondary osteoporosis, but the mechanism underlying its development is unclear. In the present study, we used prednisolone to treat zebrafish larvae to investigate GIOP. Our RNA deep-sequencing (RNA-seq) results show that prednisolone affects genes known to act in the extracellular region. Therefore the extracellular region, extracellular matrix, and collagen trimer might be involved in glucocorticoid-induced osteoporosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the focal adhesion signaling pathway is the most enriched signaling pathway in terms of differentially expressed genes (DEGs). In this pathway, integrin subunit alpha 10 (itga10) and integrin subunit beta like 1 (itgbl1), genes encoding two adapter proteins, were down-regulated in the prednisolone-treated larvae. Further experiments showed that prednisolone contributes to GIOP by down-regulating itga10 and itgbl1

Targeting strategies for bone diseases: signaling pathways and clinical studies

Abstract Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting strategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of the classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key membrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug delivery, different delivery strategies targeting bone matrix, bone marrow, and specific bone cells are summarized with a comparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area

miR-1 Inhibits the Ferroptosis of Chondrocyte by Targeting CX43 and Alleviates Osteoarthritis Progression

Dysregulation of miRNAs in chondrocytes has been confirmed to participate in osteoarthritis (OA) progression. Previous study has screen out several key miRNAs may play crucial role in OA based on bioinformatic analysis. Herein, we identified the downregulation of miR-1 in OA samples and inflamed chondrocytes. The further experiments revealed that miR-1 played an essential role in maintaining chondrocytes proliferation, migration, antiapoptosis, and anabolism. Connexin 43 (CX43) was further predicted and confirmed to be the target of miR-1, and mediated the promotion effects of miR-1 in regulating chondrocyte functions. Mechanistically, miR-1 maintained the expression of GPX4 and SLC7A11 by targeting CX43, attenuated the accumulation of intracellular ROS, lipid ROS, MDA, and Fe2+ in chondrocytes, thereby inhibiting the ferroptosis of chondrocytes. Finally, experimental OA model was constructed by anterior cruciate ligament transection surgery, and Agomir-1 was injected into the joint cavity of mice to assess the protective effect of miR-1 in OA progression. Histological staining, immunofluorescence staining and Osteoarthritis Research Society International score revealed that miR-1 could alleviate the OA progression. Therefore, our study elucidated the mechanism of miR-1 in OA in detail and provided a new insight for the treatment of OA

Supplementary excel 1

This file contains all the difference expression genes from RNA-seq analysis. This file was made with excel 201

gene expression data

This file contains data of gene expression data from qRT-PCR. This file was made with Microsoft excel 2010

Supplementary excel 3

This file contains KEGG pathway results which enriched by DEGs of RNA-seq. This file was made with Microsoft excel 201