Inflammatory Joint Disorders Research Articles

Integrating multiomics and Single-Cell communication analysis to uncover Ankylosing spondylitis mechanisms

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory joint disorder, necessitating early diagnosis and effective treatment. The specific mechanism of action of Cassia twigs in the treatment of AS is not fully understood. MethodsBlood samples and clinical data from 28,458 individuals (6,101 with AS, 22,357 without AS) were collected. To construct a predictive model, we utilized logistic regressions and machine learning techniques to create a dynamic nomogram. Immune cell infiltration was evaluated using the GSE73754 dataset. Subsequently, we obtained vertebral bone marrow blood from AS patients for 10X single-cell sequencing. We also extracted and purified total RNA from hip joint ligament tissue samples from six AS patients and six non-AS patients. The genes related to the expression of AS and Cassia twigs were analyzed comprehensively, and the specific drug targets were identified by molecular docking. The interactions between immune cells through cell communication analysis were elucidated. ResultsWe developed a dynamic nomogram incorporating the neutrophil count (NEUT) and other variables. Neutrophil immune responses were confirmed through immune infiltration analysis utilizing GSE73754. We observed the early involvement of neutrophils in the pathology of AS. The CAT-expressing Cassia twigs gene could be used as a drug target for the treatment of AS. Moreover, comprehensive RNA analysis revealed notable CAT expression in neutrophils and various other immune cells. ConclusionsNeutrophils play dual roles in AS, regulating inflammation and initiating differentiation signals to other cells. The CAT gene, which is expressed in Cassia twigs, has emerged as a potential therapeutic target for AS treatment.

Metallothionein-1 mitigates the advancement of osteoarthritis by regulating Th17/Treg balance

Osteoarthritis (OA) is a chronic inflammatory joint disorder characterized by cartilage degradation and bone remodeling. This study investigated the regulatory role of metallothionein 1 (MT1) in modulating immune responses and the balance between regulatory T cells (Treg) and T helper 17 cells (Th17) in OA. Peripheral blood mononuclear cells (PBMCs) from healthy individuals and OA patients were assessed for cytokine expression linked to Treg/Th17 homeostasis. OA was induced in wild-type (WT) and Mt1 knockout (MT1KO) mice via surgical destabilization of the medial meniscus. Clinical scores, pathological features, inflammatory cytokines, and Treg/Th17 balance were evaluated. MT1KO mice showed significantly elevated Mt1, pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and exacerbated OA progression, characterized by increased knee joint diameter, inflammatory infiltration, and cartilage destruction. Mechanistically, disrupted Treg/Th17 balance played a pivotal role in OA exacerbation, with MT1KO promoting Th17 differentiation and reducing Treg populations. Additionally, the compensatory elevation of anti-inflammatory interleukin-10 (IL-10) in OA patients hinted at a nuanced immune regulatory mechanism. The study illuminates intricate interactions involving MT1, Treg/Th17 cells, and pro-inflammatory cytokines in OA pathogenesis, suggesting MT1′s potential as a pivotal regulatory factor and a therapeutic target for mitigating immune dysregulation in OA.

Sinapic acid-pullulan based inflammation responsive nanomicelles for the local treatment of experimental inflammatory arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints. It is one of the major causes of disability and morbidity worldwide. Administration of conventional drugs through the systemic route restricts the bioavailability of drugs, systemic toxicity, and reduced efficacy. We have introduced Rebamipide (Reb)-loaded Sinapic acid (SA)-Pullulan (PL) nanomicelles (Reb@SA-PL NMs), a nanotechnology based drug delivery system for the treatment of inflammatory arthritis. PL is a polysaccharide obtained from the fungus Aureobasidium pullulans, and SA is a bioactive polyphenol found in various plants. Both are classified by US-FDA Generally Recognised as Safe (GRAS) materials. Reb@SA-PL NMs found to be cytocompatible. Subsequently, intra-articular administration of Reb@SA-PL NMs enhances the anti-arthritic potential compared to free Reb drug in collagen-induced experimental inflammatory arthritis rat model. Reb@SA-PL NMs reduced the expression of RANKL receptor and Nf-κB. Reb@SA-PL NMs reverses the breakdown of type II collagen, MMP-13, and inhibits the pro-inflammatory markers. Reb@SA-PL NMs prevented bone erosion, cartilage degradation, joint oedema, and synovial inflammation. The results of the study demonstrated that Reb@SA-PL NMs, an enzyme-responsive drug delivery system, has excellent potential for alleviating inflammatory arthritis by blocking MMP-13 and RANKL.

Connexin 43 Modulation in Human Chondrocytes, Osteoblasts and Cartilage Explants: Implications for Inflammatory Joint Disorders.

Connexin 43 (Cx43) is crucial for the development and homeostasis of the musculoskeletal system, where it plays multifaceted roles, including intercellular communication, transcriptional regulation and influencing osteogenesis and chondrogenesis. Here, we investigated Cx43 modulation mediated by inflammatory stimuli involved in osteoarthritis, i.e., 10 ng/mL Tumor Necrosis Factor alpha (TNFα) and/or 1 ng/mL Interleukin-1 beta (IL-1β), in primary chondrocytes (CH) and osteoblasts (OB). Additionally, we explored the impact of synovial fluids from osteoarthritis patients in CH and cartilage explants, providing a more physio-pathological context. The effect of TNFα on Cx43 expression in cartilage explants was also assessed. TNFα downregulated Cx43 levels both in CH and OB (-73% and -32%, respectively), while IL-1β showed inconclusive effects. The reduction in Cx43 levels was associated with a significant downregulation of the coding gene GJA1 expression in OB only (-65%). The engagement of proteasome in TNFα-induced effects, already known in CH, was also observed in OB. TNFα treatment significantly decreased Cx43 expression also in cartilage explants. Of note, Cx43 expression was halved by synovial fluid in both CH and cartilage explants. This study unveils the regulation of Cx43 in diverse musculoskeletal cell types under various stimuli and in different contexts, providing insights into its modulation in inflammatory joint disorders.

Pharmaceutical Preparation of Amrita Guggulu and its Clinical Efficacy on Vatarakta

This study scrabbles about into the pharmaceutical preparation of Amrita Guggulu, a traditional Ayurvedic formulation known for its therapeutic properties. The focus of the research is on assessing the clinical efficacy of Amrita Guggulu in managing Vatarakta, a condition characterized by vitiated Vata as well as Pitta and associated with inflammatory joint disorders. The pharmaceutical preparation involves meticulous formulation techniques, ensuring the quality and potency of the final product. Standardization parameters include the selection of authentic raw materials, adherence to traditional preparation methods and quality control measures. Clinical Trial Design: The clinical trial was designed as a randomized, double-blind study to assess the efficacy of Amrita Guggulu in patients diagnosed with Vatarakta. Participants were randomly assigned to either the treatment group receiving Amrita Guggulu group A or group B. A comprehensive clinical trial was conducted to evaluate the efficacy of Amrita Guggulu in patients diagnosed with Vatarakta. Key parameters such as joint pain, inflammation in joint, tenderness, burning sensation in affected area, skin rashes and tingling sensation were selected for the study. Overall improvement was assessed using standardized tools and patient-reported outcomes. Result: Preliminary findings indicate promising results, suggesting that Amrita Guggulu may play a significant role in alleviating symptoms associated with Vatarakta. The observed effects include a reduction in joint pain, improved joint function, and decreased inflammatory markers. Conclusion: This research contributes valuable insights into the pharmaceutical preparation of Amrita Guggulu and highlights its potential as an effective intervention for Vatarakta. On the basis of this clinical trial, we can say that S. Uric acid is not the confirmatory parameter for the decision of Vatarakta (gout). Further studies and long-term observations are recommended to solidify these findings and establish Amrita Guggulu as a viable therapeutic option in managing inflammatory joint disorders.

Musculoskeletal imaging of senescence.

Senescent cells play a vital role in the pathogenesis of musculoskeletal (MSK) diseases, such as chronic inflammatory joint disorders, rheumatoid arthritis (RA), and osteoarthritis (OA). Cellular senescence in articular joints represents a response of local cells to persistent stress that leads to cell-cycle arrest and enhanced production of inflammatory cytokines, which in turn perpetuates joint damage and leads to significant morbidities in afflicted patients. It has been recently discovered that clearance of senescent cells by novel "senolytic" therapies can attenuate the chronic inflammatory microenvironment of RA and OA, preventing further disease progression and supporting healing processes. To identify patients who might benefit from these new senolytic therapies and monitor therapy response, there is an unmet need to identify and map senescent cells in articular joints and related musculoskeletal tissues. To fill this gap, new imaging biomarkers are being developed to detect and characterize senescent cells in human joints and musculoskeletal tissues. This review article will provide an overview of these efforts. New imaging biomarkers for senescence cells are expected to significantly improve the specificity of state-of-the-art imaging technologies for diagnosing musculoskeletal disorders.

IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.

The concept of osteoarthritis (OA) as a low-grade inflammatory joint disorder has been widely accepted. Many inflammatory mediators are implicated in the pathogenesis of OA. Interleukin (IL)-18 is a pleiotropic cytokine with versatile cellular functions that are pathogenetically important in immune responses, as well as autoimmune, inflammatory, and infectious diseases. IL-17, a proinflammatory cytokine mainly secreted by Th17 cells, is upregulated in OA patients. However, the role of IL-17 in OA progression is unclear. The synovial tissues collected from healthy donors and OA patients were used to detect the expression level of IL-18 by IHC stain. The OA synovial fibroblasts (OASFs) were incubated with recombinant IL-17 and subjected to Western blot, qPCR, and ELISA to examine IL-18 expression level. The chemical inhibitors and siRNAs which targeted signal pathways were used to investigate signal pathways involved in IL-17-induced IL-18 expression. The microRNAs which participated IL-18 expression were surveyed with online databases miRWalk and miRDB, followed by validation with qPCR. This study revealed significantly higher levels of IL-18 expression in synovial tissue from OA patients compared with healthy controls, as well as increased IL-18 expression in OASFs from rats with severe OA. In vitro findings indicated that IL-17 dose-dependently promoted IL-18 production in OASFs. Molecular investigations revealed that the MEK/ERK/miR-4492 axis stimulated IL-18 production when OASFs were treated with IL-17. This study provides novel insights into the role of IL-17 in the pathogenesis of OA, which may help to inform OA treatment in the future.

Enteropathic SAPHO Syndrome in Ulcerative Colitis Responsive to Bisphosphonates

SAPHO syndrome, a rare inflammatory disorder of bone, joints, and skin, is named based on the presence of synovitis, acne, pustulosis, hyperostosis, and osteitis. The hallmark of SAPHO syndrome includes osteoarticular and dermatologic manifestations, however, rarer associations with inflammatory bowel disease (particularly Crohn’s disease) have been documented. The literature on the relationship between SAPHO syndrome and inflammatory bowel disease (IBD), especially ulcerative colitis (UC), remains limited. We report an unusual case of SAPHO syndrome in a patient with UC. Chest x‐ray and MRI showed enlargement of the right first rib and adjacent sternum. Bone scintigraphy revealed hyperostosis and ankylosis of the costochondral junction, and bone biopsy revealed reactive bone and costal cartilage without findings of infection or malignancy. Complete resolution of symptoms was achieved 4 months after starting zoledronic acid without significant adverse events. The diagnosis of SAPHO syndrome in IBD patients is rare, even more so in UC patients, likely attributable to underdiagnosis given the clinical heterogeneity of SAPHO syndrome and overlap with the extra‐intestinal manifestation of IBD. Our treatment approach provides critical data to the underreported literature on diagnosis and managing SAPHO syndrome in UC.

A bioactive and biodegradable vitamin C stearate-based injectable hydrogel alleviates experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder affecting nearly 1% of the global population. In RA, synovial joints are infiltrated by inflammatory mediators and enzymes, leading to articular cartilage deterioration, joint damage, and bone erosion. Herein, the 9-aminoacridine-6-O-stearoyl-L-ascorbic acid hydrogel (9AA-SAA hydrogel) was formulated by the heat-cool method and further characterized for surface charge, surface morphology, rheology, and cytocompatibility. Furthermore, we evaluated the therapeutic efficacy of the 9AA-SAA hydrogel, an enzyme-responsive drug delivery system with on-and-off switching capabilities based on disease severity against collagen-induced experimental arthritis in Wistar rats. The anti-inflammatory action of the US FDA-approved drug 9-aminoacridine (9AA) was revealed which acted through nuclear receptor subfamily 4 group A member 1 (NR4A1), an anti-inflammatory orphan nuclear receptor that inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, we have explored the role of ascorbic acid, an active moiety of 6-O-stearoyl-L-ascorbic acid (SAA), in promoting the production of collagen production through ten-eleven translocation-2 (TET2) upregulation. Targeting through NR4A1 and TET2 could be the probable mechanism for the treatment of experimental arthritis. The combination of 9AA and ascorbic acid demonstrated enhanced therapeutic efficacy in the 9AA-SAA hydrogel, significantly reducing the severity of experimental arthritis. This approach, in contrast to existing treatments with limited effectiveness, presents a promising and more effective strategy for RA treatment by mitigating inflammation in experimental arthritis.

Challenges in Diagnosing Psoriatic Arthritis in Primary Care: A Meta-Ethnographic Study.

Psoriatic arthritis (PsA) is a complex and debilitating chronic inflammatory joint disorder that is often associated with psoriasis and presents significant challenges in its early diagnosis and management. Therefore, this study aimed to investigate the diagnostic intricacies of PsA in primary care settings to shed light on the prevalence, barriers, and implications of delayed diagnosis. To achieve our research objectives, we conducted a qualitative synthesis using the meta-ethnographic method, which is a robust approach for synthesizing qualitative data. We systematically searched the PubMed, Web of Science, and Embase databases for relevant articles using predefined search terms such as "psoriatic arthritis," "diagnosis," and "primary care." The inclusion criteria were narrative articles in English that provided insights into the diagnostic challenges of PsA in primary care. Conference presentations, original articles, and duplicate articles were excluded. Our analysis revealed four key themes that elucidated the multifaceted nature of PsA diagnosis in primary care: (1) a variety of initial and non-specific symptoms, highlighting the diverse clinical presentations that can mimic other conditions; (2) the lack of experience with PsA among primary care professionals, underscoring the importance of education and training; (3) the lack of skin lesions, which can complicate diagnosis when not present; and (4) a delay in diagnosis, with potentially severe consequences for patients' health and quality of life. This study highlights the challenges inherent in the diagnosis of PsA in primary care settings. The multifaceted nature of the disease, coupled with limited experience among primary care providers, often results in delayed diagnosis and subsequent treatment initiation. Early recognition and intervention are pivotal for optimizing patient outcomes. Addressing these challenges necessitates a comprehensive approach involving heightened clinical suspicion, continuous medical education, interdisciplinary collaboration, and utilization of standardized diagnostic criteria. Collaboration between primary care physicians and specialists is crucial for enhancing the accuracy and timeliness of PsA diagnosis and ultimately improving patient well-being and quality of life.

A multifunctional supramolecular hydrogel that rapidly binds TNF-α for efficient reduction of synovial inflammation and cartilage destruction in rheumatoid arthritis

TNF-α is a key inflammatory cytokine in the progression of rheumatoid arthritis (RA), which is the most common inflammatory joint disorder and is characterized by persistent synovitis and cartilage destruction. However, systematic use of TNF-α inhibitors may cause undesirable side effects and fail to repair damaged cartilage. Here we design a self-assembling Nap-DFDFDEGPIRRSDS (termed FP) peptide that can form injectable supramolecular hydrogels and inhibit TNF-α within 15 min. Following integration of metformin-loaded hollow copper sulfide (CuS/MET, termed CM) nanoparticles (NPs) into these FPCM hydrogels, invasion by RA synovial fibroblasts and polarization of pro-inflammatory M1 type macrophages is reduced by inhibiting TNF-α and releasing MET. In addition, CuS NPs are chondroinductive, allowing the hydrogels to provide a suitable microenvironment for cartilage regeneration. More importantly, intraarticular injection of FPCM hydrogels significantly alleviates synovial inflammation and promotes cartilage repair in an adjuvant-induced arthritis mouse model. The therapeutic mechanism was shown to involve inhibition of the PI3K/AKT signaling pathway. Our approach synergistically inhibits inflammation and promotes tissue repair, thus holding promise for treatment of many kinds of inflammatory arthritis where TNF-α is overexpressed.

High-resolution ultrasound and MRI in the evaluation of the forefoot and midfoot.

Radiography is the appropriate initial imaging modality to assess for midfoot and forefoot pathology before turning to advanced imaging techniques. While most lesions of the mid- and forefoot can be diagnosed clinically, the exact nature and severity of the pathology is often unclear. This review addresses the use of the ultrasound, as well as the added value of magnetic resonance imaging, in diagnosing conditions of the midfoot and forefoot. Ultrasound allows a dynamic assessment as well as enabling imaging-guided interventions for diagnostic and therapeutic purposes. Practical tips for optimal examination of this area with ultrasound and magnetic resonance imaging are provided. Metatarsal stress fracture, Chopart's injury, Lisfranc injury, as well as the 1st metatarsophalangeal joint injury and lesser metatarsophalangeal plantar plate injury are injuries unique to the mid- and forefoot. The imaging anatomy of the 1st and lesser metatarsophalangeal joints is reviewed, as such knowledge is key to correctly assessing injury of these joints. Characteristic imaging features of masses commonly encountered in the mid- and forefoot, such as ganglion cyst, Morton neuroma, gouty tophus, plantar fibroma, foreign body granuloma, and leiomyoma are reviewed. The use of ultrasound and magnetic resonance imaging in assessing degenerative and inflammatory joint disorders, and in particular rheumatoid arthritis, of the mid- and forefoot region is also reviewed. In summary, when necessary, most lesions of the mid-and forefoot can be adequately assessed with ultrasound, supplemented on occasion with radiographs, computed tomography, or magnetic resonance imaging.

Outcome Analysis of Posterior Cruciate Ligament Injuries: A Narrative Review.

The primary posterior stabilizer of the knee is the posterior cruciate ligament (PCL), the largest intra-articular ligament in the human knee. One of the four primary ligaments of the knee joint, the PCL, serves to support the tibia on the femur. An extreme force applied anteriorly to the proximal tibia of the flexed knee results in trauma to the PCL. Dashboard injuries, which occur when the knee is driven into the dashboard after a collision with a motor vehicle, are frequent causes. Grade 1 and 2 acute injuries are often addressed conservatively due to the PCL's natural capacity for mending. If a grade 3 injury occurs, a cautious trial can be conducted on elderly or low-demand patients. When standard treatment for isolated grade 3 injuries has failed, surgery is advised. Single-bundle or double-bundle techniques using either transtibial tunnel or tibial inlay techniques are among the reconstruction approaches. Restoring the natural kinematics of the knee and forestalling persistent posterior and mixed rotatory knee laxity are the ultimate goals of treating PCL injuries through a personalized strategy. These injuries may become more common in the future as more people participate in sports. As a result of ongoing instability, discomfort, diminished function, and the emergence of inflammatory and degenerative disorders of joints, PCL rips are becoming more well-acknowledged as a cause of morbidity and decreased function.

Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders.

The bile salt-stimulated lipase (BSSL) was originally recognized as a lipolytic enzyme expressed by the exocrine pancreas and in some species, notably humans, the lactating mammary gland, being secreted into the duodenum and with the mother's milk, respectively. However, BSSL is also present in the blood and has been assigned additional functions, even beyond the gastrointestinal tract. Conventional BSSL knockout mice are protected from developing disease in animal models of arthritis, and antibodies directed towards BSSL prevent or mitigate disease in similar models. The aim of this study was to investigate the role of BSSL as a newly discovered player in inflammation and specifically in inflammatory joint disorders. As part of mechanism of action, we here show that BSSL is secreted by neutrophils, interacts with monocytes and stimulates their migration in vitro. An anti-BSSL antibody that blocks the human BSSL-monocyte interaction was shown to simultaneously prevent the signaling pathway by which BSSL induce cell migration. Moreover, in this cohort study we show that BSSL levels are significantly higher in blood samples from patients with rheumatoid arthritis and psoriatic arthritis compared to healthy controls. The BSSL levels in patients' blood also correlated with disease activity scores and established inflammatory markers. Hence, although the mode of action is not yet fully clarified, we conclude that BSSL could be considered a proinflammatory component in the innate immune system and thus a possible novel target for treatment of chronic inflammation.

Prevalence of signs and symptoms related to temporomandibular disorders and orofacial pain in patients indicated for orthognathic surgery: a meta-analysis.

To evaluate the prevalence of signs and symptoms related to temporomandibular disorders (TMD) and orofacial pain in patients with indication for orthognathic surgery. The search was carried out in seven electronic databases and gray literature. Studies that evaluated the frequency of signs and symptoms related to TMD and orofacial pain were included. The risk of bias was assessed using the Joanna Briggs Critical Appraisal tool. A meta-analysis of proportions with a random effect model was performed and the GRADE tool judged the certainty of evidence. After searching the databases, 1859 references were retrieved, 18 of which were selected for synthesis. The prevalence of individuals with at least one TMD symptom was 51% [CI95% = 44-58%], and 44% of the subjects had temporomandibular joint click/crepitus [CI95% = 37-52%]. Additionally, 28% exhibited symptoms related to muscle disorders [CI95% = 22-35%], 34% had disc displacement with or without reduction [CI95% = 25-44%], and 24% had inflammatory joint disorders [CI95% = 13-36%]. The prevalence of headache was 26% [CI95% = 8-51%]. The certainty of evidence was considered very low. Approximately 1 in 2 patients with dentofacial deformity presents some sign and symptom related to TMD. Myofascial pain and headache may be present in approximately a quarter of patients with dentofacial deformity. A multidisciplinary treatment is necessary for these patients, involving a professional with expertise in the management of TMD.

GAS CHROMATOGRAPHIC-MASS SPECTROMETRIC ANALYSIS OF K.G. 101 (KSHEERAGULOOCHI 101): AN AYURVEDIC PATENT PRODUCT

K.G.101 (Ksheeraguloochi 101) is an Ayurvedic patent product manufactured by Sitaram Ayurveda Private Ltd. Thrissur, Kerala. This is widely used by practitioners in the management of joint disorders. To explain this mechanism of action, the knowledge of biomedical compounds in the product is mandatory. The present study deals with the Gas chromatographic-mass spectrometric analysis of K.G.101 to explain its medicinal value. This type of study is the need of the hour for better scientific validation and a new approach to the treatment. The Gas chromatographic-mass spectrometric profile indicated the presence of nearly 39 molecules. Most compounds show anti-inflammatory potential, which explains their action in inflammatory joint disorders. The antioxidant property of the compounds explains their rejuvenating property. Some compounds show anti-cancerous activity also, which yet has to be explored.

Alternative Approaches to Osteoarthritis-Related Knee Pain: Transvenous Arteriovenous Malformation Embolization

Background: Osteoarthritis (OA) of the knee is an inflammatory joint disorder of the cartilage, joint capsule, synovium, and surrounding bone. Intraarticular inflammation induces angiogenesis leading to pain and inflammation. Research suggests a relationship between patients with osteoarthritis of the knee and venous insufficiency or contributing arteriovenous malformations (AVMs). Similar to genicular artery embolization (GAE), transvenous or transmalformation cannulation and embolization offers a minimally invasive treatment modality for patients with mild to moderate osteoarthritis. Case presentations: Here, we present the successful treatment of OA of the knee using direct puncture transmalformation cannulation and embolization in five patients. Direct puncture, a technique used to embolize peripheral AVMs, is a safe, less invasive method for the treatment of osteoarthritis with associated AVMs. Conclusions: For patients with OA-related knee pain and associated AVMs, the advancement of endovascular techniques offers alternative approaches to the treatment of mild to moderate OA. Direct puncture and transmalformation cannulation and embolization reduce the risk of intra- and post-operative complications, improve recovery time, and minimize operating time and operating costs. In review of the literature, this is one of the first published reports describing the use of direct puncture transvenous or transmalformation cannulation and embolization to treat OA-related pain.

Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40-100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell-cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA.

Injectable Decorin/Gellan Gum Hydrogel Encapsulating Adipose-Derived Stem Cells Enhances Anti-Inflammatory Effect in Cartilage Injury via Autophagy Signaling

Adipose-derived stem cells (ADSCs) are employed as a promising alternative in treating cartilage injury. Regulating the inflammatory “fingerprint” of ADSCs to improve their anti-inflammatory properties could enhance therapy efficiency. Herein, a novel injectable decorin/gellan gum hydrogel combined with ADSCs encapsulation for arthritis cartilage treatment is proposed. Decorin/gellan gum hydrogel was prepared according to the previous manufacturing protocol. The liquid–solid form transition of gellan gum hydrogel is perfectly suitable for intra-articular injection. Decorin-enriched matrix showing an immunomodulatory ability to enhance ADSCs anti-inflammatory phenotype under inflammation microenvironment by regulating autophagy signaling. This decorin/gellan gum/ADSCs hydrogel efficiently reverses interleukin-1β-induced cellular injury in chondrocytes. Through a mono-iodoacetate-induced arthritis mice model, the synergistic therapeutic effect of this ADSCs-loaded hydrogel, including inflammation attenuation and cartilage protection, is demonstrated. These results make the decorin/gellan gum hydrogel laden with ADSCs an ideal candidate for treating inflammatory joint disorders.

STEP TOWORDS THE FORMULATION OF INJECTABLE HYDROGEL: PREFORMULATION STUDIES OF TERIFLUNOMIDE

Purpose: The aim of formulation of this hydrogel is to treat the osteoarthritis which is one of the common inflammatory autoimmune disorders of joints. The use of conventional drugs like NSAIDs having various side effects.
 The aim of our research was to develop a formulation of injectable hydrogel containing teriflunomide. This study will be helps us for the development of stable, robust and therapeutically effective dosage form.
 Method: Solubility of Teriflunomaide was determined by using various solvents. By using infrared spectrum and absorption maxima the purity of sample was checked. With the help of UV spectrophotometer standard UV curve was developed. Drug excipients compatibility studies were performed using Fourier transform infrared spectroscopy, differential scanning colorimetry, partition coefficient and also short term drug solution stability studies were performed.
 Result: Teriflunomide is soluble in methanol & 0.1 N NaOH on the other hand poorly soluble in distilled water, phosphate buffer (pH 7.4) and 0.1 N HCl. Absorption maxima was observed at 292nm and infrared spectrum was showing the characteristic peaks. The standard curve obtained was linear with correlation coefficient below 1. Log P value obtained at 2.78 it confirms that teriflunomide is having both hydrophilic & hydrophobic nature. After the entire short term stability studies drug was found to be stable in short term stability studies.
 Conclusion: The studies like melting point, FTIR etc suggested that drug selected for the formulation was found to be pure. Partition coefficient values suggested that it is having both hydrophilic and hydrophobic nature. Results obtained from short term stability studies were suggested that drug is stable showing no degradation on phosphate buffer which confirmed by no shift of λ max.