Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.

Signaling modality within gp130 receptor enhances tissue regeneration

Adult mammals are incapable of multi-tissue regeneration and augmentation of this potential may drastically shift current therapeutic paradigms. Here, we found that a common co-receptor of IL-6 cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) exhibit regenerative, not reparative, responses after wounding in skin and anti-degenerative responses in the synovial joint. In addition, pharmacological inhibition of gp130 Y814 results in regeneration of multiple tissues in several species as well as disease modification in animal models of osteoarthritis. Our study characterizes a novel molecular mechanism that, if selectively manipulated, enhances the intrinsic regenerative capacity while preventing pathological outcomes in injury and disease.

Understanding and managing pain in the arthritic synovial joint: an update

Osteoarthritis is a very common cause of chronic pain in dogs and cats. Great progress has been made in the last 2–3 decades in unravelling the molecular mediators of joint pain. Now we are starting to see the benefits of this research in terms of new targets to block joint pain and new medicines reaching our pharmacy shelves. This review summarises the progress that has been made in understanding why and how arthritic joints cause pain. This will help readers understand novel medicines and provide insight into the others that might follow in the future.

Investigating the Etiology and Diagnosis of Sacroiliac Joint Pain

The sacroiliac (SI) joint is often characterized as a large, auricular-shaped, and diarthrodial synovial joint. The SI ligamentous structure is more extensive in the dorsal part due to the absence of the posterior capsule, which functions as a connecting band between the sacrum and ilium. In addition, a network of muscles supports the SI joint that helps deliver regional muscular forces to the pelvic bones. The third and fourth decades of life promote senescent changes manifested by surface irregularities, crevice formation, fibrillation, and clumping of chondrocytes.

Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis

Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Regulatory T cell (Treg):Th17 homeostatic balance. Normoxic EVs present the optimal strategy for broad therapeutic benefit. EVs present an effective novel technology with the potential for cell-free therapeutic translation.

Modification of cognitive behavior therapy to improve the skill of elderly with osteoarthritis

One of the characteristics of physical changes in the elderly involves a decrease in the musculoskeletal system, such as the depletion of the synovial joint fluid which has an impact on the pain felt in joints. This condition can cause a disruption of the quality of life for the elderly and results in increases in the family burden. The purpose of cognitive-behavioral therapy in nurse care planning is to provide an overview of the implementation of family care nursing, community care health nursing, and management of health services by community health nurses to the elderly with osteoarthritis. The innovation and development of this senior citizen community program, initially named Lansia SMART (SMART Elderly), consists of six sessions, including psychoeducation sessions, cognitive restructuring sessions, pain management sessions with progressive muscle relaxation, activity scheduling sessions, problem-solving sessions, and tutorial sessions for the Lansia SMART (SMART Elderly) group with the Android application. The final maintaining challenging stage of these services involved 59 elderly participants. Data analysis used paired T-tests. The results of this innovation showed significant differences in the behavior of the elderly participants after the implementation of the SMART Elderly program (p < 0.05). The SMART Elderly program was effective to improve the elderly participants’ behavior. Nurses can use cognitive behavioral therapy to improve the process of self-management of osteoarthritis among their clients.

Bioprinting of biomimetic self-organised cartilage with a supporting joint fixation device

Despite sustained efforts, engineering truly biomimetic articular cartilage (AC) via traditional top-down approaches remains challenging. Emerging biofabrication strategies, from 3D bioprinting to scaffold-free approaches that leverage principles of cellular self-organisation, are generating significant interest in the field of cartilage tissue engineering as a means of developing biomimetic tissue analogues in vitro. Although such strategies have advanced the quality of engineered cartilage, recapitulation of many key structural features of native AC, in particular a collagen network mimicking the tissue’s ‘Benninghoff arcade’, remains elusive. Additionally, a complete solution to fixating engineered cartilages in situ within damaged synovial joints has yet to be identified. This study sought to address both of these key challenges by engineering biomimetic AC within a device designed to anchor the tissue within a synovial joint defect. We first designed and fabricated a fixation device capable of anchoring engineered cartilage into the subchondral bone. Next, we developed a strategy for inkjet printing porcine mesenchymal stem/stromal cells (MSCs) into this supporting fixation device, which was also designed to provide instructive cues to direct the self-organisation of MSC condensations towards a stratified engineered AC. We found that a higher starting cell-density supported the development of a more zonally defined collagen network within the engineered tissue. Dynamic culture was implemented to further enhance the quality of this engineered tissue, resulting in an approximate 3 fold increase in glycosaminoglycan and collagen accumulation. Ultimately this strategy supported the development of AC that exhibited near-native levels of glycosaminoglycan accumulation (>5% WW), as well as a biomimetic collagen network organisation with a perpendicular to a parallel fibre arrangement (relative to the tissue surface) from the deep to superficial zones via arcading fibres within the middle zone of the engineered tissue. Collectively, this work demonstrates the successful convergence of novel biofabrication methods, bioprinting strategies and culture regimes to engineer a hybrid implant suited to resurfacing AC defects.

Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common form of chronic synovial joint inflammation in children. It potentially leads to disability and psychosocial outcomes for children and their families. In the absence of appropriate treatment, this can lead to joint destruction and disability. Thus, early diagnosis and aggressive treatment are essential. With the presentation of new biologic DMARDs, based on understanding the disease pathophysiology and molecular pathogenesis, the course of the disease and its outcome have been changed profoundly. In this chapter, the early diagnosis, appropriate treatment, and outcomes approaches are described. These include the latest diagnosis and management options.

NOVEL NANO THERAPEUTIC MATERIALS FOR THE EFFECTIVE TREATMENT OF RHEUMATOID ARTHRITIS-RECENT INSIGHTS

Recent advances in science and technology and greatly modified the way we stumble on, deal with and prevent special diseases in all components of human lifestyles. Rheumatoid arthritis (RA) is the most not unusual complex multifactorial joint related autoimmune, chronic, severe systemic inflammatory ailment with unknown etiology completed with increased cardiovascular risks. It is regularly associated with critical synovial joint inflammation, autoantibody production, cartilage/bone tissue destruction, cardiovascular, pulmonary, skeletal disorders and massive inflammatory infiltration which might in the end motive extreme disability, huge complications, premature mortality and decreased life quality. Pro-inflammatory cytokines like IL-1, IL-6, IL-8 and IL-10 were dependable for the induction of inflammation in RA patients. It has a global occurrence of around 1% with the incidence among women being 2-3 times extra in men. Preclinical RA, genetic variables, and environmental factors have all been linked to the disease's etiology. Because there is no known cure for RA, the primary goal of treatment is to achieve the shortest possible illness duration and, if possible, rehabilitation. Current clinical remedies of RA display numerous drawbacks which include excessive doses, common administration, speedy metabolism, bad absorption, low responsiveness, higher cost and serious side consequences. These obstacles have inspired extremely good growth of the studies and to enhance those obstacles, nanoparticles that are able to encapsulating and protecting tablets from degradation earlier than they reach the target site in vivo, might also function drug delivery structures. Bioavailability and therapeutic bioactivity can be improved, and limited emphasis on damaged joints can be allowed. The current study provides a platform for different lipid nanoparticle methods for RA therapy, using the newly developing field of lipid nanoparticles to improve a targeted theranostic device for RA treatment. This review aims to present the most recent major application of lipid nanoparticles as a biocompatible and biodegradable transport device for improving RA concentration on over free drugs by presenting tissue-specific concentrated on of ligand-controlled drug release by modulating nanoparticle composition. Additionally, we also discuss the pivotal demanding situations to be addressed, as well as destiny views. Therefore, it is feasible to claim that nanoparticles will, within the near future, play a critical role in advanced treatment and affected person-particular cures for human diseases which include RA.

Nox2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis

Osteoarthritis (OA) is a destructive disease of the joint with age and obesity being its most important risk factors. Around 50% of OA patients suffer from inflammation of the synovial joint capsule, which is characterized by increased abundance and activation of synovial macrophages that produce reactive oxygen species (ROS) via NADPH-oxidase 2 (NOX2). Both ROS and high blood levels of low-density lipoprotein (LDL) are implicated in OA pathophysiology, which may interact to form oxidized LDL (oxLDL) and thereby promote disease. Therefore, targeting NOX2 could be a viable treatment strategy for OA. Collagenase-induced OA (CiOA) was used to compare pathology between wild-type (WT) and Nox2 knockout (Nox2−/−) C57Bl/6 mice. Mice were either fed a standard diet or Western diet (WD) to study a possible interaction between NOX2-derived ROS and LDL. Synovial inflammation, cartilage damage and ectopic bone size were assessed on histology. Extracellular ROS production by macrophages was measured in vitro using the Amplex Red assay. Nox2−/− macrophages produced basal levels of ROS but were unable to increase ROS production in response to the alarmin S100A8 or the phorbol ester PMA. Interestingly, Nox2 deficiency reduced cartilage damage, synovial lining thickness and ectopic bone size, whereas these disease parameters were not affected by WD-feeding. These results suggest that NOX2-derived ROS are involved in CiOA development.