Articular Damage Research Articles

Disease Damage in Juvenile Idiopathic Arthritis.

To estimate the prevalence and predictors of disease-related damage in children with juvenile idiopathic arthritis (JIA) in a resource-limited setting. A single-centre study was conducted from January 2021 - December 2022. Children (≤ 18 y) diagnosed with JIA as per International League of Associations for Rheumatology (ILAR) criteria, with a disease duration of more than one year, were enrolled for this study. The articular and extra-articular damage was assessed using the juvenile arthritis damage index (JADI) and modified JADI scores. Disease activity and disabilities were evaluated using the clinical juvenile arthritis disease activity score (cJADAS) and Childhood Health Assessment Questionnaire (CHAQ). One hundred and five children [44% (n = 42) boys] with JIA were enrolled in the study. The mean (SD) age of children at enrolment was 158 (46.2) mo. The median (IQR) disease duration was 48 (36-72) mo. Articular damage (JADI score ≥ 1) was present in 48.6%, and extra-articular damage (JADI-E ≥ 1) was observed in 21.9% of children. Half of the children (n = 22) with enthesitis-related arthritis (ERA) had joint damage (modified JADI score ≥ 1). Four children had ocular damage due to uveitis. Among the factors associated with articular damage, the odds of articular damage were high in those with positive rheumatoid factor (RF) and/ or anti-cyclic citrullinated peptides (CCPs) [OR: 4.4, 95% CI (1.00-19.60)]. 48.6% of children with JIA had articular damage, while 21.9% of the children had extra-articular damage. Children with RF and/ or anti-CCP positivity are associated with higher odds of joint damage.

Articular Surface Damage Following Headless Intramedullary Nail Fixation of Proximal Phalanx Fractures

Offering the benefits of rigid fixation while minimizing soft tissue dissection, intramedullary implants have become a popular choice among hand surgeons. Their placement often requires traversing or passing in proximity to joint surfaces. This study aimed to assess the damage to the articular cartilage of the base of the proximal phalanx resulting from antegrade placement of threaded headless intramedullary nails. A cadaveric study comparing two techniques for antegrade placement of threaded headless intramedullary nails was conducted in 56 digits. The first entailed a single 2.1 mm intramedullary nail placed via the dorsal base of the proximal phalanx, whereas the second used two 1.8 mm intramedullary nails inserted via the collateral recesses of the phalangeal base. All specimens were analyzed for articular surface damage with the cartilage defect measured as a percentage of total joint surface area. Damage to the extensor tendons was also assessed in a subset of specimens. No significant difference in the percentage of articular surface damage was observed, with an average 3.21% ± 2.34% defect in the single 2.1 mm nail group and a 2.71% ± 3.42% mean defect in the two 1.8 mm nails group. There was no articular surface injury in 18% of digits in each group. Damage to extensor tendons was seen in three (9.4%) specimens and in all cases involved either the extensor indicis proprius or extensor digiti minimi. Hardware insertion using either the dorsal base of the proximal phalanx or the collateral recesses of the phalangeal base both demonstrated minimal articular cartilage damage and infrequent injury to the extensor tendons. With proper technique for antegrade insertion into the proximal phalanx, the cartilage defect observed often encompasses only a small percentage of the overall joint surface area.

Prevalence of Articular Surface Injuries in Patients Undergoing Meniscal Surgery: A Retrospective Analysis of 758 Cases.

Background and aim Meniscal tears are often associated with articular surface damage, which could be an important factor in the clinical outcome. However, these concomitant lesions are usually reported as binary variables. Reports of the severity/extent of the concomitant lesions and stratification by meniscal tear are scarce in the literature; in addition, sample sizes of previous reports are limited. This study aimed to characterize meniscal lesions, determine the prevalence of articular surface lesions and their severity, and correlate these lesions with meniscal injury characteristics. Methods A cross-sectional study of patients undergoing meniscal surgery between 2017 and 2023 was conducted. Patient characteristics and arthroscopic findings on the location and type of meniscal injury as well as the degree of chondral lesion (sICRS score) were recorded by the surgeon. Statistical analysis included frequency reporting for patient characteristics and study variables, including the median and interquartile range of the sICRS classification of articular surface lesions. Meniscal tear types were categorized as degenerative or non-degenerative to explore associations with chondral injury. Chi-squaretestand univariate and multivariate logistic regression models were employed to analyze relationships between variables. Results A total of 758 surgeries were analyzed, with a mean age of 39.56 years (SD: 12.71) and 67.90% male participants. Medial meniscus injuries accounted for 57.52%, lateral meniscus 36.02%, and both menisci 6.64%. Significant differences were found in vascular area, topography, and lesion type between isolated medial and lateral meniscus lesions (p<0.01). Chondral lesions were present in 35.22% of cases, with significant differences among meniscal injury types (p<0.01). Degenerative tears showed higher rates of chondral damage compared to non-degenerative tears, particularly in lateral meniscus injuries (p<0.01). Regression analysis identified age, gender, meniscal injury characteristics, and meniscectomy percentage as risk factors for articular surface injuries. Conclusion Articular surface injuries frequently accompany meniscal lesions, with associations between affected menisci and articular damage extent. Femoral condyles show greater involvement corresponding to compartment-specific meniscal lesions, unlike tibial plateaus. Meniscal degeneration is present in about half of articular cartilage injury cases. Some meniscal tear types may relate to more severe articular lesions, but larger studies are needed to confirm these findings and explore other tear patterns.

Nonunion of distal humeral fractures: Current concepts

The incidence of complex articular fractures of the distal humeral in adults has increased and will be growing in the future due to the greater incidence of high energy trauma and to the higher percentage of elderly population. Successful treatment is challenging for the needed balance between a stability of often comminuted fracture and early motion.Nonunion is a common complication after distal humerus fractures that is influenced by a variety of factors such as biology, in particular the blood supply of the metaphysis, the non-anatomical reduction of the fracture, the methods of fixation, and mechanical failure. These can involve the intra-articular or extra-articular areas. Clinical presentation may be mainly with a flail elbow in extra-articular nonunion or mainly with disfunction and stiffness for an intra-articular nonunion. However, the symptoms will depend on the degree of articular surfaces damage and the main localization of nonunion in the intra- and extra-articular region. The surgical treatment is usually required, being the non-operative treatment with a brace a reasonable option just for low-demand patients and with a high risk of complications. Despite a limited range of motion regained, the union rate achieved with internal fixation and bone grafting is substantially high.

PENGARUH KONSUMSI REBUSAN DAUN SALAM SEBAGAI ANTIINFLAMASI TERHADAP NYERI SENDI OSTEOARTHRITIS

Osteoarthritis (OA) is a joint disorder that affects all parts of the joint, especially cartilage, can have an impact on articular structural damage and loss of synovial joint function as well as causing chronic pain and requires treatment that has minimal side effects and cheap, so research on bay leaves has been carried out as an alternative solution. The research aims to determine the impact of consuming boiled bay leaves as an anti-inflammatory in reducing osteoarthritis pain. Quasi-experimental research design, use pretest posttest group design approach. Pain measurement uses the NRS scale. Samples were taken with a total sampling of 38 osteoarthritis sufferers in Wates Village. Data analysis using the Wilcoxon sign rank test with an interpretation error rate of α = 0.05. The result was that almost half of the respondents, 17 people (44.7%) experienced a decrease in the pain scale to mild pain after being given the consumption of bay leaf decoction with a P value = 0.000, meaning that there was an effect of consuming bay leaf decoction on reducing pain in osteoarthritis patients. Bay leaf bioled has effects on reducing pain in osteoarthritis sufferers because bay leaves contain tannins, flavonoids, alkaloids and essential oils, while flavonoids play an active role as anti-inflammatory by inhibiting transcription factors such as NF-κB. Inhibition of NFκB is part of the activity of flavonoids in inflammatory responses. This is similar to transcription factor and activation protein-1 (AP-1). Keywords: Anti-Inflammatory; Bay Leaf Boiled; Osteoarthritis; Pain

In vitro and in vivo studies of the therapeutic potential of Tinospora crispa extracts in osteoarthritis: Targeting oxidation, inflammation, and chondroprotection

Ethnopharmacological relevanceThe increasing incidence of osteoarthritis (OA), especially among the elderly population, highlights the need for more efficacious treatments that go beyond mere symptomatic relief. Tinospora crispa (L.) Hook. f. & Thomson (TC) boasts a rich traditional heritage, widespread use in Ayurveda, traditional Chinese medicine (TCM), and diverse indigenous healing practices throughout Southeast Asia for treating arthritis, rheumatism, fever, and inflammation. Aim of the studyThis study investigates the anti-inflammatory and chondroprotective potential of TC stem extracts, including ethanolic TC extract (ETCE) and aqueous TC extract (ATCE), in modulating OA pathogenesis through in vitro and in vivo approaches. Materials and methodsThe study utilized LC-MS/MS to identify key compounds in TC stem extracts. In vitro experiments assessed the antioxidative and anti-inflammatory properties of ETCE and ATCE in activated macrophages, while an in vivo monoiodoacetate (MIA)-induced OA rat model evaluated the efficacy of ETCE treatment. Key markers of oxidative stress, such as superoxide dismutase (SOD) and catalase (CAT), were assessed alongside pro-inflammatory cytokines TNF-α and IL-1β, and matrix-degrading enzymes, matrix metalloproteinase (MMP 13 and MMP 3), to evaluate the therapeutic effects of TC stem extracts on OA. ResultsChemical profiling of the extracts was conducted using LC-MS/MS in positive ionization, identifying seven compounds, including pseudolaric acid B, stylopine, and reticuline, which were reported for the first time in this species. The study utilized varying concentrations of TC stem extracts, specifically 6.25–25 μg/mL for in vitro assays and 500 mg/kg for in vivo studies. Our findings also revealed that both ETCE and ATCE exhibit dose-dependent reduction in reactive oxygen species (41%–52%) and nitric oxide (NO) levels (50% and 72%), with ETCE displaying superior antioxidative efficacy and marked anti-inflammatory properties, significantly reducing TNF-α and IL-6 at concentrations above 12.5 μg/mL. In the MIA-induced OA rat model, ETCE treatment notably outperformed ATCE, markedly lowering TNF-α (1.91 ± 0.37 pg/mL) and IL-1β (26.30 ± 3.68 pg/mL) levels and effectively inhibiting MMP 13 and MMP 3 enzymes. Furthermore, macroscopic and histopathological assessments, including ICRS scoring and OARSI grading, indicate that TC stem extracts reduce articular damage and proteoglycan loss in rat knee cartilage. These results suggest that TC stem extracts may play a role in preventing cartilage degradation and potentially alleviating inflammation and pain associated with OA, though further studies are needed to confirm these effects. ConclusionThis study highlights the potential of TC stem extracts as a novel, chondroprotective therapeutic avenue for OA management. By targeting oxidative stress, pro-inflammatory cytokines, and cartilage-degrading enzymes, TC stem extracts promise to prevent cartilage degradation and alleviate inflammation and pain associated with OA.

Malunion of distal humeral fractures: Current concepts

The incidence of complex articular fractures of the distal humeral in adults has increased and will be growing in the future due to the greater incidence of high-energy trauma and to the higher percentage of the elderly population. Successful treatment is challenging for the needed balance between the stability of often comminuted fractures and early motion.Malunion is a common complication after distal humerus fractures that is influenced by a variety of factors, such as biology, particularly the blood supply of the metaphysis, the nonanatomical reduction of the fracture, the methods of fixation, and mechanical failure. These can involve the intra-articular or extra-articular areas. The clinical presentation may be mainly with pain and instability as for the cubitus varus, or with disfunction and stiffness as for an intra-articular malunion. However, the symptoms will depend on the degree of articular surfaces damage and the degree of deformities in specific planes. The surgical treatment can be challenging, varying from supracondylar osteotomies and re-contouring arthroplasty for extra-articular deformities to interposition arthroplasty, and elbow replacement for intra-articular deformities.

NS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway

Articular cartilage damage and chondrocyte apoptosis are among the distinguishing features of osteoarthritis. (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) is a transient receptor potential cation channel subfamily M member 7 (TRPM7) channel inhibitor and was initially considered a potent inhibitor of small-conductance Ca2+-activated K+ channels(SK1-3 or KCa2.1–2.3 channels). Since SK is one of the targets for atrial fibrillation therapy, several studies have been conducted using NS8593 and it has been shown to be effective in improving atrial fibrillation in rats, dogs and horses. Recently, inhibition of TRPM7 has been reported to alleviate articular cartilage destruction. However, the role and mechanism of NS8593 on articular chondrocyte damage is unknown. The purpose of this study was to investigate the effect and mechanism of NS8593 on sodium nitroprusside (SNP)-induced chondrocyte apoptosis in vitro. The results showed that SNP decreased cell viability and induced chondrocyte apoptosis. NS8593 dose-dependently inhibited the SNP-induced decrease in cell viability and reduced chondrocyte apoptosis. In addition, SNP stimulation significantly increased the phosphorylation level of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), and NS8593 treatment partially reversed the alteration of STING phosphorylation level. Treatment with the STING inhibitor H-151 inhibited SNP-induced chondrocyte apoptosis. These results suggest that NS8593 may inhibit SNP-induced chondrocyte apoptosis by suppressing the STING signaling pathway.

Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-β1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics.

Delay in diagnosis and therapy in patients with arthritis commonly leads to progressive articular damage. The study aimed to investigate the immunohistochemical reactivity of synovial cytokines associated with inflammation and the bone erosives/neoformatives processes among individuals diagnosed with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and radiographic axial spondyloarthritis (r-axSpA), with the intention of identifying potential biomarkers. Specimens were collected from the inflamed knee joints of patients referred for arthroscopic procedures, and the synovial tissue (ST) was prepared for quantifying protein expression through immunohistochemical analysis (% expressed in Ratio_Area-Intensity) for TGF-β1, IL-17A, Dkk1, BMP2, BMP4, and Wnt5b. The collected data underwent thorough analysis and examination of their predictive capabilities utilising receiver operating characteristic (ROC) curves. Valid synovial tissue samples were acquired from 40 patients for IHC quantification analysis. Initially, these patients had not undergone treatment with biologics. However, after 5 years, 4 out of 13 patients diagnosed with PsA and two out of nine patients diagnosed with RA had commenced biologic treatments. Individuals with early PsA who received subsequent biologic treatment exhibited significantly elevated IHC reactivity in ST for TGF-β1 (p = 0.015). Additionally, patients with both PsA and RA who underwent biologic therapy displayed increased IHC reactivity for IL-17A (p = 0.016), TGF-β1 (p = 0.009), and Dkk1 (p = 0.042). ROC curve analysis of IHC reactivity for TGF-β1, Dkk1, and IL-17A in the synovial seems to predict future treatment with biologics in the next 5 years with the area under the curve (AUC) of a combined sum of the three values: AUC: 0.828 (95% CI: 0.689-0.968; p 0.005) S 75% E 84.4%. Higher synovial immunohistochemistry reactivity of IL-17A, Dkk1, and TGF-β1 in patients with early psoriatic arthritis and rheumatoid arthritis may serve as potential indicators for predicting the necessity of utilising biologic treatments.

The Effect of Valgus Deformity Degree of Knee Osteoarthritis Patients on Tibiofemoral Angle Mechanical Output and Knee Society Score After Total Knee Arthroplasty Non-Constrained at Prof. Dr. I.G.N.G Ngoerah Hospital

Background: Osteoarthritis (OA) is a progressive musculoskeletal problem causing a loss of articular cartilage and damage to cellular and biomechanical components. In Indonesia, the prevalence of OA is 36.5 million people, with 40% over 70 years old and 80% with limited movement. Malalignment in the knee joint, found in almost 10% of patients undergoing total knee arthroplasty (TKA) surgery, is a challenge for orthopedic surgeons. Factors such as body weight, high BMI, work history, malalignment, and synovitis are associated with the development of knee OA. Total Knee Arthroplasty (TKA) is a surgical procedure to overcome OA problems in the knee joint, but deformities affect the success of TKA surgery. Researchers aim to determine if there is an association between valgus deformity in knee OA patients and tibiofemoral angle correction and Knee Society Score 12 weeks after TKA. Methods: The study involved 42 patients with primary knee osteoarthritis and valgus deformity who underwent primary Total Knee Replacement (TKR) at Prof. Dr. Ngoerah Hospital. The study included patients with grade III-IV Kellgren-Lawrence knee osteoarthritis, underwent primary TKA, and had lower extremity scans before and 12 weeks postoperatively. Functional and clinical outcomes were measured using mechanical tibiofemoral angle and Knee Severity Score. Results: The study involved 21 female patients with OA Ranawat 2 and a 7:1 ratio of male and female participants. The most common OA was in the right knee. After TKR, there was no significant difference in MTFA and KSS scores between patients. However, after 12 weeks, the average MTFA score decreased to 8.57, with a significant change before and after the surgery. Keywords: Osteoarthritis, total knee arthroplasty (TKA), Kellgren-Lawrence.

Osteoarthritis of the temporomandibularjoint

Osteoarthritis (OA) is a degenerativejoint disease marked by progressive lossof articular cartilage and damage of bony components. The clinical features include;joint pain, crepitus and limitation of movement. The exact cause of OA is unknownhowever some authors consider it as a multifaetorial disease. The age and over usageare the most common tactors, in addition to race and sex. ln case oftemporomandibular joint(TMJ), traumatic occlusion, and over load caused byparafunctions are additional factors. The purpose ofthis investigation was to study theTMJ) arthropathy among a group of Iraqi patients previously diagnosed as having(.OAOne hundred patients with OA are used in this study. They were examined.clinically and radiographically for effects of systemic OA on TMJResults of the study revealed that 39% of patients with OA have TMJ lesions ofdifferent degrees ranged between osteophytes, diminusion of joint space and bone.distruction ofglenoid fossa and head of condyleDental management of temporomandibular joints affected with OA usuallyaim to suppress the active disease, preserve functions, prevent deformity and relievepain. Early detection of the disease and early commencement of management greatly ireduce joint destruction and improve prognosis. Results of this study indicated thatl1% of patients had only TMJ lesions, with no other joints lesions. Because ofdifficulty of interpretation of TMJ radiographs we suggest criteria for radiographicdiagnosis of osteoarthritis ofthe TMJ&#x0D;

Suprapatellar tibial nailing: intraoperative arthroscopic evaluation and results at a minimum of 12 months follow-up.

To arthroscopically evaluate the intra-articular structures before and after placement of an intramedullary tibial nail using the suprapatellar approach and to assess the 1-year results. All patients with a tibial fracture that underwent intramedullary tibial nailing using the suprapatellar approach with a minimal follow-up of 12 months were included. Diagnostic intraoperative knee arthroscopy was performed before and immediately after insertion of the IMN. A radiological and clinical evaluation and VAS score of the patients was collected postoperatively. In total, 36 patients were included. The mean follow-up period was 14.9 ± 4.9 months. The mean age of the patients was 45.5 ± 18.8 years. The mean visual analog scale (VAS) score at 12 months was 1.0 ± 1.5. The complication rate was 19.4% and the reoperation rate was 16.7%. Union of the fractures was achieved in 33 patients (91.6%) after primary surgery after a mean of 6.1 ± 1.8 months. A change in the patellofemoral cartilage after insertion of the nail was seen in 1 patient. The suprapatellar procedure for tibia fractures resulted in excellent VAS scores and union rates at 1-year follow up, with a complication of articular damage to the PF joint in 2.8%.

A post hoc comparative real-world analysis of HEAD-US score for joint health assessment of patients with severe haemophilia A and B in Spain.

Joint damage due to haemarthrosis can be effectively monitored with point-of care ultrasound using the Haemophilia Early Arthropathy Detection with US (HEAD-US) scoring system. A post hoc comparative analysis of the joint status of patients with severe haemophilia A (HA) or B (HB) was performed. The databases of two observational, cross-sectional studies that recruited patients with HA or HB from 12 Spanish centres were analysed to compare the status of the elbows, knees and ankles in patients with severe disease according to treatment modality. The HEAD-US score was calculated in both studies by the same trained operators. Overall, 95 HA and 41 HB severe patients were included, with a mean age of 35.2±11.8 and 32.7±14.2 years, respectively. The percentage of patients who received prophylaxis, over on-demand (OD) treatment, was much higher in HA (91.6%) than in HB (65.8%) patients. With a similar number of target joints, the HEAD-US score was zero in 6.3% HA and 22.0% HB patients (p<.01), respectively. The HA population showed significantly worse HEAD-US scores. Whilst osteochondral damage occurred more frequently in patients OD or tertiary prophylaxis, our data suggest that articular damage is less prominent in primary/secondary prophylaxis, regardless of the type of haemophilia. These latter treatment modalities were also associated with a lower prevalence of synovial hypertrophy, particularly in HB patients. This post hoc analysis indicates that joint status seems to be significantly influenced by haemophilia type (HA or HB) and treatment modality in these severe Spanish populations with severe disease. Continuing HEAD-US monitoring for the early detection and management of intra-articular abnormalities, as well as more efficiently tailored therapies should be warranted.

Changes in type VI collagen degradation reflect clinical response to treatment in rheumatoid arthritis patients treated with tocilizumab

ObjectivesRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation in multiple articular joints, causing pain, joint damage, and loss of joint function. Despite the successful development of disease-modifying therapies, the heterogeneity of RA means that a significant proportion of patients respond poorly to treatment. This highlights the need for personalized medicine and predictive biomarkers to optimize treatment efficacy, safety, and cost. This study aimed to explore the relationship between type VI collagen (Col VI) remodeling and clinical response to anti-IL-6 receptor treatment.MethodsType VI collagen degradation was quantified using the C6M biomarker, a fragment of type VI collagen degraded by MMPs. Longitudinal differences in average biomarker levels between placebo and treatment groups were estimated using linear mixed models. The predictive capacity of the marker based on change from baseline to 4 weeks was analyzed using logistic regression.ResultsBoth 4 mg and 8 mg doses of Tocilizumab (TCZ) reduced serum C6M concentrations compared to the placebo. Furthermore, C6M levels were more reduced in patients responding to treatment compared to early non-responders. A lower early reduction in C6M was associated with reduced odds of ACR treatment response and lowered disease activity.ConclusionThese findings suggest that quantifying type VI collagen turnover may aid in identifying patients less likely to respond to treatment, indicating a new path towards optimizing patient care. Further studies are needed to validate these findings and explore the underlying mechanisms driving the observed relationships.

Bioactive components and potential mechanisms of Biqi Capsule in the treatment of osteoarthritis: based on chondroprotective and anti-inflammatory activity.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

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.

Magnetic targeting of lornoxicam/SPION bilosomes loaded in a thermosensitive in situ hydrogel system for the management of osteoarthritis: Optimization, in vitro, ex vivo, and in vivo studies in rat model via modulation of RANKL/OPG

Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt–enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 31.22 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management.Graphical

MiR-20 promotes cartilage repair in knee osteoarthritis rats via BMP2/Smad1 signaling pathway.

To explore the effect of micro ribonucleic acid (miR)-20b on knee osteoarthritis rats by regulating the bone morphogenetic protein 2 (BMP2)/Smad1 pathway, a total of 36 SD rats were randomly divided into normal group (n=12), model group (n=12) and miR-20b mimics group (n=12). The rats in normal group were fed normally, while those in model group and miR-20b mimics group were used to establish knee osteoarthritis models. After modeling, model group was not given any intervention, but miR-20b mimics group received intra-articular injection of miR-20b mimics once a day for 2 weeks. Basso, Beattie and Bresnahan (BBB) limb motor function scoring was performed at 1, 5, 7 and 14 days after the modeling, and samples were obtained after 2 weeks of intervention. Next, hematoxylin and eosin (H&E) staining was applied to observe tissue morphology, Markin's scoring was utilized to evaluate articular cartilage degeneration, and immunohistochemistry was employed to detect the expressions of BMP2 and Smad1. Thereafter, the expression of miR-20b was detected via qPCR, the content of cartilage oligomeric matrix protein (COMP) and C-telopeptide of type II collagen (CTX-II) was measured via enzyme-linked immunosorbent assay (ELISA), and the expressions of BMP2 and Smad1 proteins were examined via Western blotting (WB). BBB limb motor function scoring showed that compared with that in normal group, the BBB limb motor function score of rats in the other two groups was reduced (P<0.05). In comparison with that in model group, the BBB limb motor function score in miR-20b mimics group was increased from the 7th day after intervention (P<0.05). In addition, H&E staining results manifested that the articular surface in normal group was smooth and flat, with normal morphology, clear structure and no obvious damage. In model group, the articular surface was not smooth and uneven, and more articular cartilage fractures, morphological disorders and structural damages could be observed. Moreover, the articular surface in miR-20b mimics group was slightly damaged and smoother, and its morphology and structure were markedly improved in contrast to that in model group. The Markin's score in normal group was lower than that in model group and miR-20b mimics group (P<0.05), and it was overtly decreased in miR-20b mimics group in comparison with that in model group (P<0.05). Next, immunohistochemistry demonstrated that compared with normal group, the other two groups had lowered positive expressions of BMP2 and Smad1 (P<0.05). In comparison with model group, miR-20b mimics group exhibited notably raised positive expressions of BMP2 and Smad1 (P<0.05). Then it was found from qPCR results that the expression level of miR-20b in the other two groups was overtly reduced compared with that in normal group (P<0.05), and it was prominently elevated in miR-20b mimics group in contrast to that in model group (P<0.05). Besides, ELISA illustrated that the content of COMP and CTX-II in the cartilage tissues in the other two groups was evidently reduced compared with that in normal group (P<0.05), and it was increased prominently in miR-20b mimics group compared with that in model group (P<0.05). Finally, it was revealed by WB examination that the relative expression levels of BMP2 and Smad1 proteins in the other two groups markedly declined in comparison with those in normal group (P<0.05), and they were elevated in contrast to those in model group (P<0.05). MiR-20b can promote cartilage repair and improve articular function in knee osteoarthritis rats by up-regulating the BMP2/Smad1 signaling pathway.

Hip Disorders in Bull Riders: Clinical Observations and Outcomes of Arthroscopy.

Bull riders represent a microcosm of athletes in whom severe consequences of femoroacetabular impingement may challenge the limits of arthroscopic intervention. Observations of this cohort may provide meaningful insight into the treatment of other populations. All patients undergoing hip arthroscopy are prospectively assessed with a modified Harris Hip Score. Sixteen consecutive bull riders (21 hips) with minimum 2-year follow-up are reported. The average age was 26 years, duration of symptoms was 33 months, and follow-up was 57 months. Arc of rotational hip motion averaged 31°. All had femoroacetabular impingement (17 combined and 4 cam impingements). Among the cam impingements, 1 also had dysplasia and 1 also had borderline dysplasia. Radiographic Tönnis grades were as follows: 2 Tönnis 1; 18 Tönnis 2; and 1 Tönnis 3. All had acetabular articular damage (14 Outerbridge grade 4; 6 Outerbridge grade 3; and 1 Outerbridge grade 1). Nine underwent microfracture. Four had accompanying femoral chondral lesions (3 grade 3; 1 grade 4). There were 20 labral tears (14 repaired and 6 debrided). All but 1 (95%) improved after surgery. One bilateral case underwent conversion to resurfacing arthroplasty on one side and revision arthroscopy on the other. The average improvement was 21.3 points. Thirteen (81.25%) returned to bull riding at an average of 7 months. Among the 3 who did not return, each had undergone bilateral procedures. There were no complications. Femoroacetabular impingement can be a significant problem among bull riders. Limited range of motion, grade 4 articular damage, and Tönnis 2 radiographic changes may not preclude successful arthroscopic treatment, but advanced bilateral disease may be too much even for these hardened athletes. [Orthopedics. 2024;47(2):79-82.].

Degree of articular injury as measured by CT cross sectional area is associated with physical function following the treatment of bicondylar tibial plateau fractures.

Bicondylar tibial plateau fractures are complex injuries that commonly require surgical repair. Long-term clinical outcome has been associated with discrepancies in leg alignment, instability and condylar width abnormalities. While intuitive, the degree of articular damage at time of injury has not been linked to outcomes in patients with bicondylar tibial plateau fractures. The aim of this study was to quantify percentage of articular surface cross sectional area disruption and assess for correlation between the degree of articular injury and patient reported physical function. Retrospective cohort study at two level 1 trauma centers. 57 consecutive patients undergoing surgical repair for bicondylar tibial plateau fractures between 2013 and 2016. Preoperative CT scans were reviewed, and the percentage of articular surface disruption cross sectional area was calculated. PROMIS® scores were collected from patients at a minimum of 2years. 57 patients with an average age of 58 ± 14.3years were included. The average PROMIS® score was 45.5. There was a correlation between percentage of articular surface disruption and total PROMIS® scores (0.4, CI: 0.2-0.5, p = .007) and the physical function of the PROMIS® score (0.4, CI: 0.2-0.6, p < .001). Our method for calculating articular surface disruption on CT is a simple, reproducible and accurate method for assessing the degree of articular damage in patients with bicondylar tibial plateau fractures. We found that the percentage of cross-sectional articular surface disruption correlates with patient reported outcomes and physical function.