TBK1-medicated DRP1 phosphorylation orchestrates mitochondrial dynamics and autophagy activation in osteoarthritis.

Mitochondrial dynamics, including mitochondrial fission and fusion, are critical for maintaining mitochondrial functions. Evidence shows that TANK-binding kinase 1 (TBK1) regulates mitochondrial fusion and fission and then mitophagy. Since a previous study demonstrates a strong correlation between mitophagy and osteoarthritis (OA), we herein investigated the potential role of TBK1 in OA process and mitochondrial functions. We demonstrated a strong correlation between TBK1 and OA, evidenced by significantly downregulated expression of TBK1 in cartilage tissue samples of OA patients and in the chondrocytes of aged mice, as well as TNF-α-stimulated phosphorylation of TBK1 in primary mouse chondrocytes. TBK1 overexpression significantly attenuated TNF-α-induced apoptosis and abnormal mitochondrial function in primary mouse chondrocytes. Furthermore, TBK1 overexpression induced remodeling of mitochondrial morphology by directly phosphorylating dynamin-related protein 1 (DRP1) at Ser637, abolishing the fission of DRP1 and preventing its fragmentation function. Moreover, TBK1 recruitment and DRP1 phosphorylation at Ser637 was necessary for engulfing damaged mitochondria by autophagosomal membranes during mitophagy. Moreover, we demonstrated that APMK/ULK1 signaling contributed to TBK1 activation. In OA mouse models established by surgical destabilization of the medial meniscus, intraarticular injection of lentivirus-TBK1 significantly ameliorated cartilage degradation via regulation of autophagy and alleviation of cell apoptosis. In conclusion, our results suggest that the TBK1/DRP1 pathway is involved in OA and pharmacological targeting of the TBK1-DRP1 cascade provides prospective therapeutic benefits for the treatment of OA.

Treatment of Intraosseous Ganglion Cyst of the Lunate: A Systematic Review.

PURPOSE: Intraosseous ganglion cyst (IGC) is a rare disease, particularly in lunate. The objective of this study was to summarize current knowledge on the treatment of IGC of the lunate, through a literature review, to provide a therapeutic strategy for this rare disease. METHODS: The PubMed, ISI Web of Science, Cochrane Library, EMBASE, Science Direct database were searched with a set of predefined inclusion and exclusion criteria. Manual searches for references were performed to find potential relevant studies. The authors extracted data from the articles selected. RESULTS: Different treatment modalities of IGC of the lunate were described, all of which were divided into 3 categories: conservative treatment, classical surgical procedures, and novel surgical procedures. An overview on the main treatment modalities for IGC of the lunate was provided. CONCLUSIONS: Conservative treatments can be the doctors' first choice for patients with IGC. Surgical procedure is advised when conservative treatment fails. Traditional surgical curettage with autologous bone grafting is the mainstay of treatment with satisfactory outcomes; however, novel surgical techniques like arthroscopically assisted minimally invasive technique or filling with bone cement are considered as more promising attempts with less trauma and shorter recovery period. Nonetheless, studies with high levels of evidence are guaranteed for developing widely accepted clinical treatment guidelines.

Comparison of Open Surgery Versus Minimally Invasive Surgery in Nonsevere Adult Degenerative Scoliosis: A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: This study aimed to evaluate the clinical efficacy of minimally invasive surgery (MIS) and open surgery in correcting ADS. SUMMARY OF BACKGROUND DATA: Adult degenerative scoliosis (ADS) is a scoliosis secondary to degenerative changes in the intervertebral discs and facet joints in adults. Severe low back pain, radicular pain, and intermittent claudication are often present and require surgical treatment. METHODS: PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI) Database, Wanfang Data, Weipu Database, and China Biomedical Document Service System (CBM) were systematically searched for studies that focused on the clinical efficacy of minimally invasive surgery and open surgery to correct ADS. RESULTS: This meta-analysis included 11 studies, involving 1527 patients (581 in the MIS group and 946 in the open surgery group). Regarding surgery and outcome indicators, the operative time in the open surgery group was shorter, the MIS group had less intraoperative blood loss, shorter hospitalization time, and lower incidence of serious postoperative complications. In terms of imaging parameters, although there was no significant difference in Cobb angle improvement and sagittal balance, the open surgery group exhibited better lumbar lordosis improvement and pelvic tilt improvement. In terms of clinical scores, including changes in the ODI index and VAS scores for low back and leg pain, similar improvements were appreciated across both groups. CONCLUSIONS: In mild to moderate ADS, we found that the advantages of open surgery include greater improvement in lumbar lordosis and pelvic tilt angle and shorter operative time. The advantages of minimally invasive surgery are less intraoperative blood loss, shorter hospital stay, and fewer serious postoperative complications. There is no significant difference between the 2 surgical methods in terms of Cobb angle, clinical pain, and sagittal vertical axis improvement.

Isoliquiritigenin mitigates intervertebral disc degeneration induced by oxidative stress and mitochondrial impairment through a PPARγ-dependent pathway.

OBJECTIVES: Oxidative stress, mitochondrial dysfunction, and apoptosis play significant roles in the degradation of extracellular matrix (ECM) in nucleus pulposus cells (NPCs), ultimately contributing to intervertebral disc degeneration (IVDD). This study investigates the potential of isoliquiritigenin (ISL), a natural extract known for its antioxidant, anti-inflammatory, and anti-atherosclerotic properties, to alleviate IVDD. METHODS: The viability of NPCs treated with ISL and tert-butyl hydroperoxide (TBHP) was assessed using the CCK-8 assay. Various techniques, including Western blot, qRT-PCR, immunofluorescence (IF), and immunohistochemistry, were employed to measure the expression of ECM components, oxidative stress markers, and apoptosis-related proteins. Mitochondrial function was evaluated through Western blot and IF analyses. Network pharmacology predicted ISL targets, and the expression levels of PPARγ were assessed using the aforementioned methods. The role of PPARγ in the therapeutic effects of ISL on IVDD was examined through siRNA knockdown. The therapeutic impact of ISL on puncture-induced IVDD in rats was evaluated using X-ray, MRI, and histological staining techniques. RESULTS: In vitro, ISL reduced oxidative stress in NPCs, restored mitochondrial function, inhibited apoptosis, and improved the ECM phenotype. In vivo, ISL slowed the progression of IVDD in a rat model. Further analysis revealed that ISL enhances PPARγ activity and promotes its expression by direct binding, contributing to the delay of IVDD progression. CONCLUSION: This study demonstrates that ISL effectively treats puncture-induced IVDD in rats by inhibiting oxidative stress, restoring mitochondrial function, and reducing NPC apoptosis through a PPARγ-dependent mechanism. By balancing ECM synthesis and degradation, ISL presents a novel therapeutic approach for IVDD and identifies a promising target for treatment.

A water strider-inspired intestinal stent actuator for controllable adhesion and unidirectional biofluid picking.

Soft-bodied aquatic organisms exhibit extraordinary navigation and mobility in liquid environments which inspiring the development of biomimetic actuators with complex movements. Stimulus-responsive soft materials including hydrogels and shape-memory polymers are replacing traditional rigid parts that leading to dynamic and responsive soft actuators. In this study, we took inspiration from water strider to develop a biomimetic actuator for targeted stimulation and pH sensing in the gastrointestinal tract. We designed a soft and water-based Janus adhesive hydrogel patch that attaches to specific parts of the intestine and responds to pH changes through external stimulation. The hydrogel patch that forms the belly of the water strider driver incorporates an inverse opal microstructure that enables pH responsive behavior. The hydrogel patch on the water strider's leg uses a sandwich structure of Cu particles to convert light into heat and bend under infrared light to mimic the water strider's leg simulating the efficient and steady movement of the water strider's leg which transporting the biological fluid in one direction. This miniature bionic actuator demonstrates controlled adhesion and unidirectional biofluid delivery capabilities, proving its potential for targeted stimulus response and pH sensing in the gastrointestinal tract, thus opening up new possibilities for medical applications in the growing field of soft actuators.

Bioinspired colloidal crystal hydrogel pressure sensors with Janus wettability for uterus cervical canal tension perception.

The pursuit of flexible, sensitive, and cost-effective pressure sensors plays a pivotal role in medical diagnostics, particularly in the domain of cervical health monitoring. However, significant challenges remain in the economical production of flexible piezoresistive materials and the integration of microstructures aimed at enhancing sensor sensitivity. This urge highlights the use of innovative, stable hydrogel films that demonstrate robust adherence to soft biological tissues, thereby enabling prolonged bio-signal monitoring. In this study, we introduce an innovative integration of a flexible pressure electrical signal sensor with structural color hydrogel scaffolds. This integration leverages the tunability of the inverse opal structure to fine-tune the scaffold's adherence to the endocervical wall under varying environmental conditions and to amplify the sensitivity of pressure measurements. Our findings indicate that this novel approach holds promise for substantial enhancements in the manufacturing and functional capabilities of cervical pressure sensors, potentially revolutionizing personalized medical treatments and improving patient monitoring.

Implantable Resistive Strain Sensor-Decorated Colloidal Crystal Hydrogel Catheter for Intestinal Tract Pressure Sensing.

In the quest to develop advanced monitoring systems for intestinal peristaltic stress, this study introduces a groundbreaking approach inspired by nature's sensory networks. By the integration of novel materials and innovative manufacturing techniques, a multifunctional Janus hydrogel patch has been engineered. This unique patch not only demonstrates superior stress-sensing capabilities in the intricate intestinal environment but also enables adhesion to wet tissue surfaces. This achievement opens new avenues for real-time physiological monitoring and potential therapeutic interventions in the realm of gastrointestinal health.

Screening of NSAIDs library identifies Tinoridine as a novel ferroptosis inhibitor for potential intervertebral disc degeneration therapy.

Low back pain (LBP) may profoundly impact the quality of life across the globe, and intervertebral disc degeneration (IVDD) is the major cause of LBP; however, targeted pharmaceutical interventions for IVDD are still lacking. Ferroptosis is a novel form of iron-dependent programmed cell death. Studies have showed that ferroptosis may closely associate with IVDD; thus, targeting ferroptosis may have great potential for IVDD therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for LBP, while nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key inhibitory protein for ferroptosis. In the current study, we conducted a molecular docking screening between NSAIDs library and Nrf2 protein. Tinoridine was shown to have a high binding affinity to Nrf2. The in vitro study in nucleus pulposus (NP) cells showed that Tinoridine may promote the expression and activity of Nrf2, it may also rescue RSL3-induced ferroptosis in NP cells. Knockdown of Nrf2 reverses the protective effect of Tinoridine on RSL3-induced ferroptosis in NP cells, suggesting that the inhibitory effect of Tinoridine on ferroptosis is through Nrf2. In vivo study demonstrated that Tinoridine may attenuate the progression of IVDD in rats. As NSAIDs are already clinically used for LBP therapy, the current study supports Tinoridine's application from the view of ferroptosis inhibition.

An Octopus-Inspired Stimulus-Responsive Structural Color Hydrogel for Uterus Cervical Canal Stent.

Soft-bodied aquatic organisms have exhibited remarkable capabilities in navigating and moving within liquid environments serving as a profound inspiration for the development of bionic robots with intricate movements. Traditional rigid components are being replaced by stimulus-responsive soft materials such as hydrogels and shape memory polymers, leading to the creation of dynamically responsive soft robots. In this study, the development of a bionic robot inspired by the shape of an octopus and the adsorptive properties of its tentacles, specifically tailored for targeted stimulation and pH sensing in the cervix, are presented. This approach involves the design of a soft, water-based Janus adhesive hydrogel patch that adheres to specific parts of the cervix and responds to pH changes through external stimuli. The hydrogel patch incorporates inverse opal microstructures mimicking the legs of an octopus, to facilitate efficient and stable locomotion, unidirectional transport of biofluids, and pH-responsive behavior. This miniature bionic robot showcases controlled adhesion and precise unidirectional fluid transport highlighting its potential for targeted stimulus response and pH sensing in the uterine cervical tract. This breakthrough opens new avenues for medical applications within the expanding field of soft-bodied robotics.

Colloidal crystals array enabled bionic biliary stent for efficient domestic biofluid management.

In vivo surgical interventions require effective management of biofluids, including controlling bleeding and removing excess biofluids such as bile, wound exudate, and blood. To address these issues, recent advances have emerged, such as self-sealing needles, drug-eluting stents, and shear-thinning hydrogels. However, complications associated with intestinal mucosal injury and secondary damage still persist. Therefore, a multifunctional stent is urgently required that can effectively remove excessive biofluid. Surface wettability of biliary stents is crucial in biofluid management, and conventional coatings can cause adhesion to wound tissue. To overcome this issue, we developed an interpenetrating Janus wettability stent coating, enabling unidirectional draining of excessive biofluid from its hydrophobic side to hydrophilic side, thereby preventing biofluid from wetting the wound. Furthermore, we demonstrate a directional biofluid movement using a self-pumping dressing in an infected tissue model, providing a new approach for in situ biofluid collection and disease diagnosis by detecting metal ion changes. Overall, our integrated system presents an opportunity to design wound dressings with effective biofluid management and metal ion detection capabilities.

Chrysophanol prevents IL-1ß-Induced inflammation and ECM degradation in osteoarthritis via the Sirt6/NF-κB and Nrf2/NF-κB axis.

Osteoarthritis (OA) is a common joint illness that negatively impacts people's lives. The main active ingredient of cassia seed or rhubarb is chrysophanol. It has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that chrysophanol has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, chrysophanol inhibited IL-1ß -induced expression of ADAMTS-4, MMP13, COX-2 and iNOS. Meanwhile, it can inhibit aggrecan and collagen degradation in osteoarthritic chondrocytes induced by IL-1ß.Further studies depicted that SIRT6 silencing eliminated the chrysophanol effect on IL-1ß. The results demonstrated that chrysophanol could stimulate SIRT6 activation and, more importantly, increase SIRT6 levels. We also discovered that chrysophanol might impede the NF-κB pathway of OA mice's chondrocytes induced by IL-1ß, which could be because it depends on SIRT6 activation to some extent. It had also been previously covered that chrysophanol could produce a marked effect on Nrf2/NF-κB axis [1]. Therefore, we can infer that chrysophanol may benefit chondrocytes by regulating the SIRT6/NF-κB and Nrf2/NF-κB signaling axis.We examined the anti-inflammatory mechanism and the impact of chrysophanol on mice in vitro and in vivo. In summary, we declare that chrysophanol diminishes the inflammatory reaction of OA in mice in vitro by regulating SIRT6/NF-κB and Nrf2/NF-κB signaling pathway and protects articular cartilage from degradation in vivo. We can infer that chrysophanol could be an efficient therapy for OA.

Orientin inhibits inflammation in chondrocytes and attenuates osteoarthritis through Nrf2/NF-κB and SIRT6/NF-κB pathway.

Effects of Orientin on murine chondrocytes treated with interleukin-1ß (IL-1ß) were evaluated using qPCR, western blot analysis, ELISA, and immunofluorescent staining in vitro. In vivo, We established a standard OA model by performing the destabilized medial meniscus (DMM) surgery on C57BL/6 mice, and assessed healing effect of Orientin by X-ray imaging, histopathological analysis, immunohistochemical staining. Osteoarthritis (OA) is the most common form of degenerative joint disease in clinic and the chondrocyte inflammation plays the most important role in OA development. The natural flavonoid compound (Orientin) has anti-inflammatory bioactive properties in the treatment of various diseases. But studies have not explored whether Orientin modulates OA progression. In this study, a significant suppression in IL-1ß-mediated pro-inflammatory mediators and the degradation of cartilage extracellular matrix (ECM) was observed in vitro through qPCR, western blot analysis, ELISA, and immunofluorescent staining after the treatment with Orientin. In addition, Orientin abrogated DMM surgery induced cartilage degradation in mice, which was assessed by X-ray imaging, histopathological analysis, immunohistochemical staining. Mechanistic studies showed that Orientin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and SIRT6 signaling pathway. These results provide evidence that Orientin serves as a potentially viable compound for the treatment of OA.

Bioinspired hierarchical colloidal crystal paper with Janus wettability for oil/water separation and heavy metal ion removal.

Increasing attention has been paid recently to superwettability and its prospective potential applications in various fields. A new approach towards the establishment of flexible, self-assembled superhydrophobic surfaces with self-reported wettability on a variety of substrates has been advanced. The approach involves the fabrication of a dense monolayer of photonic crystal films that possess a layered structure with superior adhesion at the liquid-gas-solid interface. Thus, the resulting hierarchical photonic crystal film with a structurally hydrophobic surface offers a promising addition to the creation of durable and flexible superhydrophobic surfaces across a variety of substrates that exhibit the self-reported wettability. Furthermore, a bifunctional membrane that can effectively remove oil and adsorb heavy metal ions contained in wastewater has been developed for potential use in large-scale industrial wastewater treatment. This research sheds fresh light on the application of bionics and the lotus and mussel functions in oil/water separation.

Bioinspired conductive structural color hydrogels as a robotic knuckle rehabilitation electrical skin.

Electronic skins have attracted significant research interest in the biomedical engineering field including wearable devices, artificial prostheses, software robots, and so on. However, the integration of electronic skin for use in rehabilitation exercise remains unexplored. Here, we propose a novel, conductive structurally colored composite hydrogel for use as a robotic knuckle rehabilitation skin. It was found that the composite structure has an obvious color variation and electromechanical properties during the bending process. Therefore, this film could be used as a multi-signal response electronic skin to achieve real-time color sensing and electrical response, as well as for the human knuckle rehabilitation robot. These results indicated that the structurally colored composite hydrogels are valuable for use in many practical biomedical rehabilitation exercises where they are used as an electronic skin to give real-time color sensing and electrical response, and as well can be used in a human knuckle rehabilitation robot.

The Potential Role of Cytokines in Diabetic Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain. Diabetes mellitus is a chronic inflammatory disease that may cause or aggravate IVDD; however, the mechanism by which diabetes induce IVDD is currently unclear. Compared to non-diabetic individuals, diabetic patients have higher levels of plasma cytokines, especially TNF-α, IL-1ß, IL-5, IL-6, IL-7, IL-10, and IL-18. Due to the crucial role of cytokines in the process of intervertebral disc degeneration, we hypothesized that elevation of these cytokines in plasma of diabetic patients may be involved in the process of diabetes-induced IVDD. In this review, changes in plasma cytokine levels in diabetic patients were summarized and the potential role of elevated cytokines in diabetes-induced IVDD was discussed. Results showed that some cytokines such as TNF-α and IL-1ß may accelerate the development of IVDD, while others such as IL-10 is supposed to prevent its development. Apoptosis, senescence, and extracellular matrix metabolism were found to be regulated by these cytokines in IVDD. Further studies are required to validate the cytokines targeted strategy for diabetic IVDD therapy.

Tangeretin suppresses osteoarthritis progression via the Nrf2/NF-κB and MAPK/NF-κB signaling pathways.

BACKGROUND: Osteoarthritis (OA) is a globally prevalent degenerative disease characterized by extracellular matrix (ECM) degradation and inflammation. Tangeretin is a natural flavonoid that has anti-inflammatory properties. Studies have not explored whether tangeretin modulates OA development. PURPOSE: The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of tangeretin. STUDY DESIGN: Effects of tangeretin on OA were detected in chondrocytes and OA mouse model. METHODS: Protective effects of tangeretin on murine articular chondrocytes treated with interleukin-1ß (IL-1ß) were evaluated using qPCR, western blot analysis, ELISA, ROS detection and immunofluorescent staining in vitro. Healing effect of tangeretin on cartilage degradation in mice was assessed through X-ray imaging, histopathological analysis, immunohistochemical staining and immunofluorescent staining in vivo. RESULTS: Tangeretin suppressed IL-1ß-mediated inflammatory mediator secretion and degradation of ECM in chondrocytes. The results showed that tangeretin abrogated destabilized medial meniscus (DMM)-induced cartilage degradation in mice. Mechanistic studies showed that tangeretin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and suppressing MAPK signaling pathway. CONCLUSION: Tangeretin abrogates OA progression by inhibiting inflammation as well as ECM degradation in chondrocytes and animal models. Effects of tangeretin are mediated through Nrf2/NF-κB and the MAPK/NF-κB pathways. Thus, tangeretin is a potential therapeutic agent for osteoarthritis treatment.

Corynoline Alleviates Osteoarthritis Development via the Nrf2/NF-κB Pathway.

Purpose: OA is a multifactorial joint disease in which inflammation plays a substantial role in the destruction of joints. Corynoline (COR), a component of Corydalis bungeana Turcz., has anti-inflammatory effects. Materials and Methods: We evaluated the significance and potential mechanisms of COR in OA development. The viabilities of chondrocytic cells upon COR exposure were assessed by CCK-8 assays. Western blot, qPCR, and ELISA were used to assess extracellular matrix (ECM) degeneration and inflammation. The NF-κB pathway was evaluated by western blot and immunofluorescence (IF). Prediction of the interacting proteins of COR was done by molecular docking, while Nrf2 knockdown by siRNAs was performed to ascertain its significance. Micro-CT, H&E, Safranin O-Fast Green (S-O), toluidine blue staining, and immunohistochemical examination were conducted to assess the therapeutic effects of COR on OA in destabilization of medial meniscus (DMM) models. Results: COR inhibited ECM degeneration and proinflammatory factor levels and modulated the NF-κB pathway in IL-1ß-treated chondrocytes. Mechanistically, COR bound Nrf2 to downregulate the NF-κB pathway. Moreover, COR ameliorated the OA process in DMM models. Conclusion: We suggest that COR ameliorates OA progress through the Nrf2/NF-κB axis, indicating COR may have a therapeutic potential for OA.

α-Cyperone (CYP) down-regulates NF-κB and MAPKs signaling, attenuating inflammation and extracellular matrix degradation in chondrocytes, to ameliorate osteoarthritis in mice.

Inflammation and extracellular matrix (ECM) degradation have been implicated in the pathological process of osteoarthritis (OA). α-Cyperone is the main active component of the traditional Chinese medicine Cyperus rotundus L. In this study, we found that α-Cyperone abolished the IL-1ß-induced production of inflammatory cytokines in isolated rat chondrocytes, such as cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), in a dose-dependent manner (0.75, 1.5 or 3 µM). Also, the results showed that α-Cyperone downregulated the expression of metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS5), and upregulated the expression of type-2 collagen. Mechanistically, molecular docking tests revealed that α-Cyperone stably and effectively binds to p65, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). α-Cyperone inhibited NF-κB activation by blocking its nuclear transfer, and decreasing the phosphorylation of mitogen-activated protein kinase (MAPKs). In addition, in vivo studies based on a mouse model of arthritis showed that α-Cyperone prevented the development of osteoarthritis. Therefore, α-Cyperone may be a potential anti-OA drug.

18ß-Glycyrrhetinic acid inhibits IL-1ß-induced inflammatory response in mouse chondrocytes and prevents osteoarthritic progression by activating Nrf2.

Osteoarthritis (OA) is presently the most prevalent form of chronic degenerative joint disease, which is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Accumulating evidence has revealed that 18ß-glycyrrhetinic acid (18ß-GA), a major bioactive component derived from Glycyrrhiza glabra, exerts anti-inflammatory effects on several diseases. However, the anti-inflammatory effects of 18ß-GA on OA remain undetermined. The present study aimed to investigate the anti-inflammatory effects of 18ß-GA on chondrocytes and the therapeutic effects on destabilization of the medial meniscus destabilization (DMM) mouse models of OA. For the in vivo study, we randomly divided the mice into three groups: vehicle control (n = 15), sham (n = 15) and 18ß-GA (n = 15) groups, and treated them with similar doses (50 mg kg-1 day-1) of 18ß-GA or saline. Cartilage tissues were harvested from the mice for histological analyses eight weeks after operation. For the in vitro studies, mouse chondrocytes were administered with 10 ng mL-1 interleukin-1ß (IL-1ß) after being treated with 18ß-GA at various concentrations. In vitro assays revealed that treatment with 18ß-GA considerably suppressed the expression of pro-inflammatory mediators and cytokines, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), nitric oxide (NO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6), which were induced by IL-1ß. Furthermore, 18ß-GA decreased the expression of matrix-degrading proteases, including matrix metalloproteinase 13 (MMP13) and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in a concentration-dependent manner, which mediated extracellular matrix (ECM) degradation. 18ß-GA reversed aggrecan and type II collagen degradation. Furthermore, we observed that 18ß-GA significantly suppressed IL-1ß-induced nuclear factor kappa B (NF-κB) activation by activating the nuclear factor erythroid-derived 2-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in vitro and in vivo. Experiments demonstrated that 18ß-GA might alleviate the progression of OA in the DMM mouse model in vivo. The findings demonstrate that 18ß-GA reduces inflammation induced by IL-1ß in chondrocytes. Therefore, 18ß-GA could be a potential therapeutic agent for OA.

RNA-Binding Protein HuR Suppresses Inflammation and Promotes Extracellular Matrix Homeostasis via NKRF in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) has been reported to be a major cause of low back pain. Studies have demonstrated that IVDD may be dysregulated at the transcriptional level; however, whether post-transcriptional regulation is involved is still unknown. The current study aimed to illustrate the role of Human antigen R (HuR), an RNA binding protein involved in post-transcriptional regulation, in IVDD. The results showed that the expression of HuR was decreased in degenerative nucleus pulposus (NP) tissues as well as in TNF-α-treated NP cells. Downregulation of HuR may lead to increased inflammation and extracellular matrix (ECM) degradation in TNF-α-treated NP cells; however, these effects were not reversed in HuR overexpressed NP cells. Inhibition of the NF-κB signaling pathway attenuates inflammation and ECM degradation in HuR-deficient NP cells. A mechanism study showed that HuR prompted NKRF mRNA stability via binding to its AU-rich elements, and upregulation of NKRF suppressed inflammation and ECM degradation in HuR-deficient NP cells. Furthermore, we found that NKRF, but not HuR, overexpression ameliorated the process of IVDD in rats in vivo. In conclusion, HuR suppressed inflammation and ECM degradation in NP cells via stabilizing NKRF and inhibiting the NF-κB signaling pathway; NKRF, but not HuR, may serve as a potential therapeutic target for IVDD.