Inflammation In Osteoarthritis Research Articles

HSYA prevents IL‐1β‐induced human chondrocyte damage in osteoarthritis by inhibiting NF‐κB activation

AbstractThe progression of osteoarthritis (OA) requires the involvement of inflammation, in which chondrocyte damage plays a significant role. Hydroxysafflor yellow A (HSYA), the main active component in the medical and edible dual‐purpose plant safflower, has previously shown anti‐inflammatory effects in various diseases. However, the specific impact of HSYA on OA remains unclear. Here, we investigate the potential role and underlying mechanism of HSYA in chondrocyte damage during the progression of OA. The viability of C28/I2 and iCell‐0092a chondrocytes was measured by CCK8 assay at different concentrations (2.5, 10, 40, and 160 μM). The gene expression of the extracellular matrix was revealed by q‐PCR 24 h after IL‐1β treatment. ROS production and levels of pro‐inflammatory cytokines in C28/I2 cells treated with HSYA were measured by immunoflurescence stating and q‐PCR. The impact of HSYA on the extracellular matrix and inflammation in IL‐1β‐induced OA were detected by western blot, q‐PCR, and immunofluorescence staining. We assessed the effect of HSYA and NF‐κB signaling pathway‐related genes by bioinformatics analysis and conducted molecular docking to assess the interaction of HSYA with a combined protein residue molecule ligand. Western blot was employed to investigate NF‐κB transcription factors in chondrocyte metabolism. HSYA was found to reduce excessive ROS production induced by IL‐1β stimuli, inhibit the expression of matrix metalloproteinase 13, interleukin 6, and tumor necrosis factor‐α, and increase the expression of Type II collagen and SRY‐box transcription factor 9 (p < .05). Mechanistically, HSYA interacted with nuclear factor κB, inhibiting the nuclear translocation and phosphorylation level of NF‐κB p65, and decreasing the phosphorylation and degradation of IκBα (p < .05). In conclusion, HSYA ameliorates inflammation and cartilage damage in OA by inhibiting the NF‐κB pathway, suggesting its potential application as a therapeutic agent for OA treatment.

Loss of effective lubricating viscosity is the primary mechanical marker of joint inflammation in equine synovitis.

Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro-inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. However, the relationship between key biochemical markers of joint inflammation and mechanical function of SF is not well understood. Here, we demonstrate the application of a novel analytical framework to measure the effective viscosity for SF lubrication of cartilage, which is distinct from conventional rheological viscosity. Notably, in a well-established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000-fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (r = -0.6 to -0.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E2 (PGE2 ), and chemokine ligand (CCLs) concentrations, while conventional measurements of viscosity were poorly correlated to these markers. These findings demonstrate the importance of experimental and analytical approaches to characterize functional lubricating properties of synovial fluid and their relationships to soluble biomarkers to better understand the progression of OA.

Injectable Ozone-Rich Nanocomposite Hydrogel Loaded with D-Mannose for Anti-Inflammatory and Cartilage Protection in Osteoarthritis Treatment.

Osteoarthritis (OA) is a dynamic condition characterized by cartilage damage and synovial inflammation. Ozone (O3) shows potential therapeutic effects owing to its anti-inflammatory properties; however, its high reactivity and short half-life substantially limit its effectiveness in OA treatment. In this study, an ozone-rich thermosensitive nanocomposite hydrogel loaded with D-mannose is developed for OA treatment. Briefly, O3 is encapsulated in nanoparticles (NPs) composed of perfluorotributylamine and fluorinated hyaluronic acid to improve its stability. Next, D-mannose is conjugated with α-amino of the hydroxypropyl chitin (HPCH) via Schiff base to prepare MHPCH. These nanoparticles are encapsulated in MHPCH to produce O3 NPs@MHPCH. In vitro cell experiments demonstrate that the O3 NPs@MHPCH treatment significantly reduced VEGF and inflammation levels, accompanied by a decrease in inflammatory factors such as IL-1β, IL-6, TNF-α, and iNOS. Furthermore, O3 NPs@MHPCH promotes the expression of collagen II and aggrecan and stimulates chondrocyte proliferation. Additionally, in vivo studies show that O3 NPs@MHPCH significantly alleviated OA by reducing synovial inflammation, cartilage destruction, and subchondral bone remodeling. O3 NPs@MHPCH offers a promising option for improving the efficacy of O3 therapy and reducing the risk of synovial inflammation and cartilage degeneration in OA.

Molecular Foundations of Inflammatory Diseases: Insights into Inflammation and Inflammasomes.

Inflammatory diseases are a global health problem affecting millions of people with a wide range of conditions. These diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), osteoarthritis (OA), gout, and diabetes, impose a significant burden on patients and healthcare systems. A complicated interaction between genetic variables, environmental stimuli, and dysregulated immune responses shows the complex biological foundation of various diseases. This review focuses on the molecular mechanisms underlying inflammatory diseases, including the function of inflammasomes and inflammation. We investigate the impact of environmental and genetic factors on the progression of inflammatory diseases, explore the connection between inflammation and inflammasome activation, and examine the incidence of various inflammatory diseases in relation to inflammasomes.

THE ROLE OF PERICYTES IN REGULATING CARTILAGE DEGRADATION AND FIBROSIS

Pericytes are contractile, motile cells that surround the capillary. Recent studies have shown that pericytes promoted joint fibrosis and induced subchondral bone angiogenesis, indicating the role of pericytes in osteoarthritis (OA). However, whether pericytes are involved in regulating inflammatory and catabolic response, as well as fibrotic repair of cartilage is still unclear. Here we used 2D and 3D models to investigate the communication of pericytes and chondrocytes under inflammatory osteoarthritis conditions.CD34-CD146+ pericytes were isolated and sorted from human bone marrow. Human OA chondrocytes were isolated from OA joints. In 2D studies, monolayer cultured chondrocytes were treated +/- pericyte conditioned media, +/- 1ng/ml IL1β for 24h. In 3D studies, pericytes and chondrocytes were cultured within fibrin gel in 3D polyurethane scaffolds, separately or combined for 7 days, followed by treatment of +/- IL1β for another 7 days (Fig 2A). The inflammatory response, catabolic activity and expression of fibrosis markers of chondrocytes and pericytes were measured by ELISA and/or q-rtPCR.Pericytes had weak inflammatory, catabolic and fibrotic response to IL1β (data not shown). The 2D study showed that pericyte conditioned media promoted inflammation, catabolism and fibrosis markers of chondrocytes, in the absence of IL1β treatment (Figure 1). However, study in 3D showed that coculture of chondrocytes and pericytes reduced the inflammatory and catabolic response of chondrocytes to IL1β and induced fibrosis markers in chondrocytes (Figure 2).Pericytes are involved in regulating inflammatory response, catabolic response and fibrosis of chondrocytes. The opposite results from 2D and 3D experiments indicate the variety of the regulatory role of pericytes in the interaction with chondrocytes within different culture models. The underlying mechanism is under evaluation with on-going studies.AcknowledgementsThis study was funded by SINPAIN project, from European Union's Horizon Europe research and innovation programme under Grant Agreement NO. 101057778. Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them.For any figures or tables, please contact the authors directly.

Deciphering the Role of LncRNAs in Osteoarthritis: Inflammatory Pathways Unveiled.

Long non-coding RNA (LncRNA), with transcripts over 200 nucleotides in length, play critical roles in numerous biological functions and have emerged as significant players in the pathogenesis of osteoarthritis (OA), an inflammatory condition traditionally viewed as a degenerative joint disease. This review comprehensively examines the influence of LncRNA on the inflammatory processes driving OA progression, focusing on their role in regulating gene expression, cellular activities, and inflammatory pathways. Notably, LncRNAs such as MALAT1, H19, and HOTAIR are upregulated in OA and exacerbate the inflammatory milieu by modulating key signaling pathways like NF-κB, TGF-β/SMAD, and Wnt/β-catenin. Conversely, LncRNA like MEG3 and GAS5, which are downregulated in OA, show potential in dampening inflammatory responses and protecting against cartilage degradation by influencing miRNA interactions and cytokine production. By enhancing our understanding of LncRNA' roles in OA inflammation, we can better leverage them as potential biomarkers for the disease and develop innovative therapeutic strategies for OA management. This paper aims to delineate the mechanisms by which LncRNA influence inflammatory responses in OA and propose them as novel targets for therapeutic intervention.

Cell Reprogramming Strategies for Treating Osteoarthritis and Intervertebral Disc Degeneration.

Osteoarthritis (OA) and intervertebral disc degeneration (IVDD) are the most common degenerative bone and joint diseases, posing a major threat to patients' physical and mental health due to the occurrence of chronic pain and disability. Within this context, the absence of efficacious therapies has led to a growing interest in regenerative medicine. In particular, as a method that can erase the memory of differentiation and re-endow cells with pluripotency, cell reprogramming technologies have ushered in a new era of personalized therapy, which not only show great potential for the treatment of degenerative osteoarthropathies but also promise to achieve tissue regenerative and repair. However, compared to other areas of research, reprogramming technologies to treat OA and IVDD are still in the preliminary stages and require further investigation. This paper briefly introduces the characteristics of cell reprogramming; summarizes the pathological mechanisms of reprogramming to improves energy metabolism, aging, inflammation, oxidative stress, and immune imbalance in OA and IVDD under the background of microenvironment and immunity; highlights the significant advantages of reprogramming-derived cells compared to embryonic stem cells and mesenchymal stem cells, based on these advances, providing important strategies for its development and clinical application in OA and IVDD.

Atipik bir artrit vakası

We present a 58-year old male patient with distal and proximal interphalangeal (DIP/PIP) joints arthritis with synovitis and dactylitis. When literature was investigated, there are a few clinical condition in which DIP involved except osteoarthritis and psoriatic arthritis. Clinical and radiologic findings are atypical for both inflammatory arthritis and osteoarthritis. A new type of hand arthritis in individuals who have tendency with findings of erosive arthritis and dactylitis may be a possible diagnosis.

Conditioned medium of IGF-1-induced human synovial membrane mesenchymal stem cells effects on inflammatory response of osteoarthritic in vitro model

Synovial membrane mesenchymal stem cells (SM-MSCs) possess excellent regenerative potential, making them a viable option for osteoarthritis (OA) therapy. Moreover, these cells can be easily obtained from the human body. Insulin-like growth factor (IGF-1) can be used to decrease the pro-inflammatory marker, these markers can trigger inflammation in OA. These challenges can be addressed by utilizing a conditioned medium (CM) derived from stem cell culture. This study aims to compare the effective way of OA therapy between CM SM-MSC and CM SM-MSC induced by IGF-1 by observe the pro-inflammatory markers such as NF-kB, RANTES, PGE2, COL1 and the anti-inflammatory marker, Aggrecan (ACAN). Chondrocyte cells induced IL-1β as OA model (IL1β-CHON002) treated with IGF-1 15% and 30% and without IGF1-induced SM-MSCs-CM to know its effectiveness in decreasing the pro-inflammatory markers. ELISA and RT-qPCR methods were performed to analyze this effect. Based on the data result, SM-MSCs-CM is estimated to have the potential to treat OA as seen from the content of growth factors in CM, decreasing the markers of inflammation. The most significant reduction in PGE2, RANTES, NF-kB, and COL1 concentration was found in the treatment of SM-MSCs-CM cultured with IGF1 concentrations of 150 ng/mL. The higher aggrecan (ACAN) concentration was found in IGF150 15%. Conclusion: CM from SM-MSCs cultured with IGF150 with concentrations of 15% and 30% resulted in the most effective concentration to decrease the concentration of pro-inflammatory markers and also to increase the anti-inflammatory markers.

The Impact of 45S5-Bioactive Glass on Synovial Cells in Knee Osteoarthritis-An In Vitro Study.

Synovial inflammation in osteoarthritis (OA) is characterized by the release of cartilage-degrading enzymes and inflammatory cytokines. 45S5-bioactive glass (45S5-BG) can modulate inflammation processes; however, its influence on OA-associated inflammation has hardly been investigated. In this study, the effects of 45S5-BG on the release of cartilage-degrading metalloproteinases and cytokines from synovial membrane cells (SM) isolated from patients with knee OA was assessed in vitro. SM were cultivated as SM monocultures in the presence or absence of 45S5-BG. On day 1 (d1) and d7 (d7), the concentrations of Matrix Metalloproteinases (MMPs) and cytokines were assessed. In 45S5-BG-treated SM cultures, MMP9 concentration was significantly reduced at d1 and d7, whilst MMP13 was significantly increased at d7. Concentrations of interleukin (IL)-1B and C-C motif chemokine ligand 2 (CCL2) in 45S5-BG-treated SM cultures were significantly increased at both time points, as were interferon gamma (IFNG) and IL-6 at d7. Our data show an effect of 45S5-BG on SM activity, which was not clearly protective, anti-inflammatory, or pro-inflammatory. The influence of 45S5-BG on MMP release was more suggestive of a cartilage protective effect, but 45S5-BG also increased the release of pro-inflammatory cytokines. Further studies are needed to analyze the effect of BGs on OA inflammation, including the anti-inflammatory modification of BG compositions.

Downregulation of Gadd45β alleviates osteoarthritis by repressing lipopolysaccharide-induced fibroblast-like synoviocyte inflammation, proliferation and migration

ObjectiveGadd45β have a regulatory role in cellular inflammation, proliferation and migration. However, the role of Gadd45β in synovial inflammation in osteoarthritis (OA) remains to be explored. This study aimed to ascertain whether Gadd45β is involved in OA synovial inflammation. MethodsThe rat model was induced by sodium iodoacetate and the cellular model was constructed with lipopolysaccharide (LPS)-induced fibroblast-like synoviocytes (FLSs). siRNA was applied to interfere with the expression of intracellular Gadd45β. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of Gadd45β mRNA and protein. The inflammation, proliferation, and migration of OA-FLSs were detected by enzyme-linked immunosorbent assay, cell scratch assay, 5-ethynyl-2′-deoxyuridine assay, etc. The effect of downregulation of Gadd45β on the nuclear factor-κB (NF-κB) pathway was investigated. ResultsExpression of Gadd45β in OA rat synovial tissues and OA-FLSs was increased, and LPS treatment promoted cell proliferation and enhanced cell migration. Gadd45β interference inhibited the inflammation, proliferation and migration of cells induced by LPS. LPS promoted P65 expression in the nucleus and activated the NF-κB signaling pathway, whereas si-Gadd45β reversed this situation. Conclusionssi-Gadd45β inhibited the inflammatory response, proliferation and migration of FLSs, and activation of the NF-κB signaling pathway, which could delay the progression of OA. Hence, it may become a potential therapeutic target for OA.

3D bioactive ionic liquid-based architectures: An anti-inflammatory approach for early-stage osteoarthritis

3D bioprinting enables the fabrication of biomimetic cell-laden constructs for cartilage regeneration, offering exclusive strategies for precise pharmacological screenings in osteoarthritis (OA). Synovial inflammation plays a crucial role in OA's early stage and progression, characterized by the increased of the synovial pro-inflammatory mediators and cytokines and chondrocyte apoptosis. Therefore, there is an urgent need to develop solutions for effectively managing the primary events associated with OA. To address these issues, a phenolic-based biocompatible ionic liquid approach, combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), was used to produce easily printable bioinks. Through the use of this strategy 3D constructs with good printing resolution and high structural integrity were obtained. The encapsulation of chondrocytes like ATDC5 cells provided structures with good cell distribution, viability, and growth, for up to 14 days. The co-culture of the constructs with THP-1 macrophages proved their ability to block pro-inflammatory cytokines (TNF-α and IL-6) and mediators (GM-CSF), released by the cultured cells. Moreover, incorporating the biocompatible ionic liquid into the system significantly improved its bioactive performance without compromising its physicochemical features. These findings demonstrate that ALG/ACE/Ch[Caffeate] bioinks have great potential for bioengineering cartilage tissue analogs. Besides, the developed ALG/ACE/Ch[Caffeate] bioinks protected encapsulated chondrocyte-like cells from the effect of the inflammation, assessed by a co-culture system with THP-1 macrophages. These results support the increasing use of Bio-ILs in the biomedical field, particularly for developing 3D bioprinting-based constructs to manage inflammatory-based changes in OA. Statement of significanceCombining natural resources with active biocompatible ionic liquids (Bio-IL) for 3D printing is herein presented as an approach for the development of tools to manage inflammatory osteoarthritis (OA). We propose combining alginate (ALG), acemannan (ACE), and cholinium caffeate (Ch[Caffeate]), a phenolic-based Bio-IL with anti-inflammatory and antioxidant features, to produce bioinks that allow to obtain 3D constructs with good printing resolution, structural integrity, and that provide encapsulated chondrocyte-like cells good viability. The establishment of a co-culture system using the printed constructs and THP-1-activated macrophages allowed us to study the encapsulated chondrocyte-like cells behaviour within an inflammatory scenario, a typical event in early-stage OA. The obtained outcomes support the beneficial use of Bio-ILs in the biomedical field, particularly for the development of 3D bioprinting-based models that allow the monitoring of inflammatory-based events in OA.

Quercitrin attenuates the progression of osteoarthritis via inhibiting NF-κB signaling pathways and enhance glucose transport capacity

Osteoarthritis (OA) is a common musculoskeletal disorder that impairs function and reduces the quality of life. Extracellular matrix (ECM) degradation and inflammatory mechanisms are crucial to the progression of OA. In this study, we aimed to investigate the anti-inflammatory activity, anti-ECM degradation property, and glucose transport capacity of quercitrin (QCT) on IL-1β-treated rat primary chondrocytes. Rat primary chondrocytes were treated with IL-1β to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of QCT at concentrations ranging from 0 to 200 μM on the viability of rat chondrocytes and selected 5 μM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model through anterior cruciate ligament transection (ACLT). The animals were then periodically injected with QCT into the knee articular cavity. Our in vivo and in vitro study showed that QCT could inhibit IL-1β-activated inflammation and ECM degradation in chondrocyte. Furthermore, QCT could inhibit the NF-κB signal pathway and enhance glucose transport capacity in the IL-1β-stimulated chondrocytes. In vivo study proved that QCT attenuates OA progression in rats. Overall, QCT inhibited the activation of NF-κB and enhanced glucose transport capacity to alleviate the progression of OA.

Forsythoside B alleviates osteoarthritis through the HMGB1/TLR4/NF-κB and Keap1/Nrf2/HO-1 pathways.

Osteoarthritis (OA) is a joint pain and dysfunction syndrome resulting from severe joint degeneration. Inflammation and degeneration of the articular cartilage are two main features of OA and have tight interactions during OA progression. Conventional treatment with nonsteroidal anti-inflammatory drugs has been widely utilized clinically, whereas the side effects have restricted their application. Forsythoside B has been found with anti-inflammatory effects and antiapoptosis in inflammatory diseases, whereas in OA it remains poorly understood. Interleukin (IL)-1β (10 ng/mL) was taken to induce an OA cell model on HC-A chondrocytes and an OA rat model was constructed for in vivo experiments. Forsythoside B was adopted to treat HC-A chondrocytes and OA rats. As shown by the data, Forsythoside B hampered IL-1β-elicited rat chondrocyte apoptosis, oxidative stress, and facilitated proliferation. The profiles of inflammatory factors, NOD-like receptor family pyrin domain containing 3 inflammasomes, Kelch-like epichlorohydrin-associated protein-1 (Keap1), and nuclear factor-κB (NF-κB) phosphorylation were suppressed by Forsythoside B, whereas the nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels were promoted. Further, Forsythoside B mitigated cartilage damage and degeneration. Moreover, the oxidative stress and inflammation mediators in the cartilage tissue of OA rats were remarkably abated. Collectively, Forsythoside B hinders the NF-κB and Keap1/Nrf2/HO-1 pathways to curb IL-1β-elicited OA rat oxidative stress and inflammation both in vivo and ex vivo, ameliorating OA development. All over, this study provides an underlying strategy for treating OA, which might help the clinical treatment of OA patients.

EPIDEMIOLOGICAL DATA REVIEW OF PRIMARY REVERSE TOTAL SHOULDER ARTHROPLASTY AT A SINGLE TERTIARY ACADEMIC HOSPITAL IN SOUTH AFRICA: A FOUR-YEAR RETROSPECTIVE REVIEW

Reverse Total shoulder arthroplasty (RTSA) was initially introduced to treat rotator cuff arthropathy. With proven successful long-term outcomes, it has gained a noteworthy surge in popularity with its indications consequently being extended to treating various traumatic glenohumeral diseases.Several countries holding national registries remain a guide to the use the prosthesis, however a notable lack of epidemiological data still exists. More so in South Africa where the spectrum of joint disease related to communicable diseases such as HIV and tuberculosis may influence indications and patient demographics. By analysing the epidemiology of patients who underwent RTSA at our institution, we aimed to outline the local disease spectrum, the patients afflicted and indications for surgery.A retrospective review of all patients operated within the sports unit between 1 January 2019 and 31 December 2022 was conducted. An analysis of the epidemiological data pertaining to patient demographics, diagnosis, indications for surgery and complications were recorded.Included in the review were 58 patients who underwent primary RTSA over the 4-year period. There were 41 females and 17 male patients, age <55 years (n= 14) >55 years (n=44). The indications included 23 rotator cuff arthropathy (40%), 12 primary glenohumeral osteoarthritis (OA) (20%), 10 avascular necrosis (AVN) humeral head (17%), 7 inflammatory OA (12%), 4 chronic shoulder dislocation (7%) and 2 sequalae of proximal humerus fractures (4%).The study revealed RTSA being performed in patients older than 55 years of age, the main pathologies included rotator cuff arthropathy and primary OA, however AVN and shoulder dislocations secondary to trauma contributed significantly to the total tally of surgeries undertaken. This highlights the disease burden of developing countries contributing to patients presenting for RTSA

The efficacy of platelet-rich plasma in treating osteoarthritis with an inflammatory phenotype: A 5-year follow up retrospective study

BackgroundWe aimed to explore whether platelet-rich plasma (PRP) can delay and reduce the incidence of total knee arthroplasty (TKA) and improve clinical symptoms in patients with inflammatory phenotype knee osteoarthritis (I-KOA). MethodsThis was a retrospective cohort study with a 5-year follow up. We selected patients with I-KOA based on typical magnetic resonance imaging findings. Patients were divided into two groups: I-KOA and KOA. Subsequently, the patients underwent treatment for five consecutive years, receiving three fortnightly injections per year, totalling 15 injections per patient. The Kellgren–Lawrence (KL) grade and minimum joint space width (MJSW) were used to evaluate KOA progression. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society score (KSS), and the minimal clinically important difference were used to evaluate the improvement of KOA symptoms. The incidence and timing of TKA were statistically analysed. ResultsIn total, 420 patients were included (I-KOA, n = 211; KOA, n = 209). No significant difference existed between both groups in the changes in the MJSW and KL grade at each time point. The I-KOA group exhibited significantly lower TKA incidence and delayed time to TKA. The WOMAC, KSS, and KSS function scores were significantly better in the I-KOA group than in the KOA group at each time point after treatment (P < 0.05). ConclusionThe results of this retrospective study suggest that, compared with conventional KOA, intra-articular injection of PRP has better efficacy in patients with I-KOA but does not delay disease progression.

Comparative Effects of Intra-Articular versus Intravenous Mesenchymal Stromal Cells Therapy in a Rat Model of Osteoarthritis by Destabilization of Medial Meniscus.

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.

Injectable Bioactive Antioxidative One-Component Polycitrate Hydrogel with Anti-Inflammatory Effects for Osteoarthritis Alleviation and Cartilage Protection.

Chronic inflammation in osteoarthritis (OA) can destroy the cartilage extracellular matrix (ECM), causing cartilage damage and further exacerbating the inflammation. Effective regulation of the inflammatory microenvironment has important clinical significance for OA alleviation and cartilage protection. Polycitrate-based polymers have good antioxidant and anti-inflammatory abilities but cannot self-polymerize to form hydrogels. Herein, a one-component multifunctional polycitrate-based (PCCGA) hydrogel for OA alleviation and cartilage protection is reported. The PCCGA hydrogel is prepared using only the PCCGA polymer by self-polymerization and exhibits multifunctional properties such as injectability, adhesion, controllable pore size and elasticity, self-healing ability, and photoluminescence. Moreover, the PCCGA hydrogel exhibits good biocompatibility, biodegradability, antioxidation by scavenging intracellular reactive oxygen species, and anti-inflammatory ability by downregulating the expression of proinflammatory cytokines and promoting the proliferation and migration of stem cells. In vivo results from an OA rat model show that the PCCGA hydrogel can effectively alleviate OA and protect the cartilage by restoring uniform articular surface and cartilage ECM levels, as well as inhibiting cartilage resorption and matrix metalloproteinase-13 levels. These results indicate that the PCCGA hydrogel, as a novel bioactive material, is an effective strategy for OA treatment and has broad application prospects in inflammation-related biomedicine.

IL-17 in osteoarthritis: A narrative review.

Osteoarthritis (OA) is a painful joint disease that is common among the middle-aged and elderly populations, with an increasing prevalence. Therapeutic options for OA are limited, and the pathogenic mechanism of OA remains unclear. The roles of cytokines and signaling pathways in the development of OA is a current research hot spot. Interleukin (IL)-17 is a pleiotropic inflammatory cytokine produced mainly by T helper 17 cells that has established roles in host defense, tissue repair, lymphoid tissue metabolism, tumor progression, and pathological processes of immune diseases, and studies in recent years have identified an important role for IL-17 in the progression of OA. This narrative review focuses on the mechanisms by which IL-17 contributes to articular cartilage degeneration and synovial inflammation in OA and discusses how IL-17 and the IL-17 signaling pathway affect the pathological process of OA. Additionally, therapeutic targets that have been proposed in recent years based on IL-17 and its pathway in OA are summarized as well as recent advances in the study of IL-17 pathway inhibitors and the potential challenges of their use for OA treatment.

Bixa orellana ethyl acetate fraction and its isolated compound ellagic acid attenuate the progression of MIA-induced osteoarthritis in rat knees

Osteoarthritis (OA) is a pathology that is characterized by progressive erosion of articular cartilage. In this context, medicinal plants have become relevant tools regarding their potential role in the prevention and treatment of OA, being safe and effective. The aim of this work was investigate the therapeutic efficacy of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc) for the therapeutic treatment of OA induced by monosodium iodoacetate (MIA) in rats. The plant material was extracted via maceration with 70 % hydroalcoholic solvent (BoHE). The ethyl acetate (BoEA) fraction was by solvents in increasing order of polarity. The ElAc was identified and isolated in BoEA using high performance liquid chromatography (HPLC-DAD) and analytical curve. The OA was induced using MIA in the right knee at the knee joint. Doses of BoEA and ElAc were administered daily (every 24 h, orally) at concentrations of 50, 100 and 50 mg/kg, respectively, for 28 days after induced OA. We evaluated the animals through clinical and radiological examinations every 7 days and, on the 29th day, the animals were euthanized, the joints being removed for histopathological analysis and the serum for cytokine analysis. BoEA and ElAc compounds reduced inflammation and nociception in OA and were as effective as indomethacin in clinical parameters of joint discomfort and allodynia in rats, in addition to showing improvements in radiological and histopathological images, acting on the progress of cartilage deterioration, proving properties related to anti-inflammatory and analgesic processes, being important allies for new therapeutic interventions for the treatment of OA.