Patient-Experience of Trapeziectomy for Trapeziometacarpal Osteoarthritis in Wide-Awake Local Anesthesia no Tourniquet, 2-Year Follow-up.

PURPOSE OF THE STUDY: The purpose of this study was to assess the patient experience of trapeziectomy under WALANT for trapeziometacarpal joint (TMJ) osteoarthritis (OA) in a prospective study with 2-year follow-up. MATERIAL AND METHODS: The study included 23 patients with TMJ OA undergoing trapeziectomy with WALANT. All patients were seen by a hand therapist preoperatively and at 3, 12, and 24 months postoperatively. At each visit, VAS pain scores, thumb range of motion, grip strength, and Disabilities of the Arm, Shoulder and Hand (DASH) score were assessed. The Picker Patient Experience (PPE-15) questionnaire was administered within 2 weeks of surgery. RESULTS: All 23 patients completed the PPE-15 questionnaire. Their mean age was 64 years. The 21 patients who remained at the 24-month follow-up all said they would choose the same anaesthesia method again. At this follow-up, VAS pain scores, thumb range of motion, key pinch grip and DASH scores had improved significantly, while thumb opposition and hand grip strength remained largely unchanged. The majority of patients felt well informed before and during the procedure, and all patients rated pain relief as good or satisfactory. Nearly 40% of patients reported receiving inadequate information about the postoperative medications. DISCUSSION: Patients have a positive attitude to trapeziectomy with WALANT, and seem to prefer WALANT over other methods of anaesthesia. Trapeziectomy with WALANT for TMJ OA is a safe procedure and appears to give a functional outcome similar to trapeziectomy under general anaesthesia. CONCLUSIONS: Trapeziectomy with WALANT for TMJ OA is safe, preferred by patients and has similar clinical outcome as trapeziectomy in general anesthesia. KEY WORDS: trapeziectomy, osteoarthritis, WALANT.

Intron retention in PI-PLC γ1 mRNA as a key mechanism affecting MMP expression in human primary fibroblast-like synovial cells.

The intron retention (IR) is a phenomenon utilized by cells to allow diverse fates at the same mRNA, leading to a different pattern of synthesis of the same protein. In this study, we analyzed the modulation of phosphoinositide-specific phospholipase C (PI-PLC) enzymes by Harpagophytum procumbens extract (HPE) in synoviocytes from joins of osteoarthritis (OA) patients. In some samples, the PI-PLC γ1 isoform mature mRNA showed the IR and, in these synoviocytes, the HPE treatment increased the phenomenon. Moreover, we highlighted that as a consequence of IR, a lower amount of PI-PLC γ1 was produced. The decrease of PI-PLC γ1 was associated with the decrease of metalloprotease-3 (MMP-3), and MMP-13, and ADAMTS-5 after HPE treatment. The altered expression of MMPs is a hallmark of the onset and progression of OA, thus substances able to decrease their expression are very desirable. The interesting outcomes of this study are that 35% of analyzed synovial tissues showed the IR phenomenon in the PI-PLC γ1 mRNA and that the HPE treatment increased this phenomenon. For the first time, we found that the decrease of PI-PLC γ1 protein in synoviocytes interferes with MMP production, thus affecting the pathways involved in the MMP expression. This finding was validated by the silencing of PI-PLC γ1 in synoviocytes where the IR phenomenon was not present. Our results shed new light on the biochemical mechanisms involved in the degrading enzyme production in the joint of OA patients, suggesting a new therapeutic target and highlighting the importance of personalized medicine.

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.

BACKGROUND: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. OBJECTIVE: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. METHODS: An injury cell model was established by treating chondrocytes with IL-1ß. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. RESULTS: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. CONCLUSION: Osteocyte-derived exosomal DLX2 alleviated IL-1ß-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.

A smart hypochlorous acid fluorescent probe enabling Ibuprofen-release for osteoarthritis theranostics.

Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro. Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.

Classification of osteoarthritic and healthy cartilage using deep learning with Raman spectra.

Raman spectroscopy is a rapid method for analysing the molecular composition of biological material. However, noise contamination in the spectral data necessitates careful pre-processing prior to analysis. Here we propose an end-to-end Convolutional Neural Network to automatically learn an optimal combination of pre-processing strategies, for the classification of Raman spectra of superficial and deep layers of cartilage harvested from 45 Osteoarthritis and 19 Osteoporosis (Healthy controls) patients. Using 6-fold cross-validation, the Multi-Convolutional Neural Network achieves comparable or improved classification accuracy against the best-performing Convolutional Neural Network applied to either the raw or pre-processed spectra. We utilised Integrated Gradients to identify the contributing features (Raman signatures) in the network decision process, showing they are biologically relevant. Using these features, we compared Artificial Neural Networks, Decision Trees and Support Vector Machines for the feature selection task. Results show that training on fewer than 3 and 300 features, respectively, for the disease classification and layer assignment task provide performance comparable to the best-performing CNN-based network applied to the full dataset. Our approach, incorporating multi-channel input and Integrated Gradients, can potentially facilitate the clinical translation of Raman spectroscopy-based diagnosis without the need for laborious manual pre-processing and feature selection.

Effect of the Sauvé-Kapandji method on the wrist contact surface for distal radial ulnar joint disorders.

BACKGROUND: The Sauvé-Kapandji (S-K) method is a surgical procedure performed for chronic deformities of the distal radial ulnar joint (DRUJ). Changes to the joint contact surface from pre- to postoperatively under physiological in vivo conditions have not yet been determined for this useful treatment. The aim of the present study was therefore to compare the articular contact area of the wrist joint between before and after the S-K method for DRUJ disorders. METHODS: The SK method was performed for 15 patients with DRUJ osteoarthritis and ulnar impaction syndrome. We calculated the Mayo Wrist Score as the patient's clinical findings and created 3-dimensional bone models of cases in which the S-K method was performed and calculated the contact area and shift in the center of the contact area using customized software. RESULTS: The Mean modified Mayo Wrist Score improved significantly from 60.3 preoperatively to 80.3 postoperatively (P < 0.01). Scaphoid contact area to the radius increased significantly from 112.6 ± 37.0 mm2 preoperatively to 127.5 ± 27.8 mm2 postoperatively (P = 0.03). Lunate contact area to radius-ulna was 121.3 ± 43.3 mm2 preoperatively and 112.5 ± 37.6 mm2 postoperatively, but this decrease was not significant (P = 0.38). Contact area ratio of scaphoid to lunate increased significantly from 1.01 ± 0.4 preoperatively to 1.20 ± 0.3 postoperatively (P = 0.02). Postoperative translations of the center of the scaphoid and lunate contact areas were decomposed into ulnar and proximal directions. Ulnar and proximal translation distances of the scaphoid contact area were 0.8 ± 1.7 mm and 0.4 ± 0.6 mm, respectively, and those of the lunate contact area were 1.1 ± 1.7 mm and 0.4 ± 1.1 mm, respectively. This study revealed changes in wrist contact area and center of the contact area before and after the S-K method. CONCLUSION: These results may accurately indicate changes in wrist joint contact area from pre- to postoperatively using the S-K method for patients with DRUJ disorder. Evaluation of changes in contact area due to bone surface modeling of the wrist joint using 3DCT images may be useful in considering surgical methods.

Dietary supplementation of vitamin B1 prevents the pathogenesis of osteoarthritis.

As the primary cause for chronic pain and disability in elderly individuals, osteoarthritis (OA) is one of the fastest-growing diseases due to the aging world population. To date, the impact of microenvironmental changes on the pathogenesis of OA remains poorly understood, greatly hindering the development of effective therapeutic approaches against OA. In this study, we profiled the differential metabolites in the synovial fluid from OA patients and identified the downregulation of vitamin B1 (VB1) as a metabolic feature in the OA microenvironment. In a murine destabilization of medial meniscus-induced OA model, supplementation of VB1 significantly mitigated the symptoms of OA. Cytokine array analysis revealed that VB1 treatment remarkably reduced the production of a pro-OA factor-C-C Motif Chemokine Ligand 2 (CCL2), in macrophages. Further evidence demonstrated that exogenous CCL2 counteracted the anti-OA function of VB1. Hence, our study unveils a unique biological function of VB1 and provides promising clues for the diet-based treatment of OA.

MiR-539-3p Alleviates Apoptosis and Extracellular Matrix Degradation in Chondrocytes of Childhood-Onset Osteoarthritis by Targeting RUNX2.

Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix etallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.

High revision rate of metal-backed glenoid component and impact on the overall revision rate of stemless total shoulder arthroplasty: a cohort study from the Danish Shoulder Arthroplasty Registry.

BACKGROUND AND PURPOSE: There is controversy regarding the results of stemmed and stemless total shoulder arthroplasty (TSA) used for osteoarthritis. Therefore, we aimed to compare revision rates of stemmed and stemless TSA and to examine the impact of metal-backed glenoid components. METHODS: We included all patients reported to the Danish Shoulder Arthroplasty Register from January 1, 2012 to December 31, 2022 with an anatomical TSA used for osteoarthritis. Primary outcome was revision (removal or exchange of components) for any reason. RESULTS: 3,338 arthroplasties were included. The hazard ratio for revision of stemless TSA adjusted for age and sex was 1.83 (95% confidence interval [CI] 1.21-2.78) with stemmed TSA as reference. When excluding all arthroplasties with a metal-backed glenoid component, the adjusted hazard ratio for revision of stemless TSA was 1.37 (CI 0.85-2.20). For the Eclipse stemless TSA system, the adjusted hazard ratio for revision of a metal-backed glenoid component was 8.75 (CI 2.40-31.9) with stemless Eclipse with an all-polyethylene glenoid component as reference. CONCLUSION:  We showed that the risk of revision of stemless TSAs was increased and that it was related to their combination with metal-backed glenoid components.

Twenty-year trajectories of morbidity in individuals with and without osteoarthritis.

OBJECTIVES: To identify multimorbidity trajectories over 20 years among incident osteoarthritis (OA) individuals and OA-free matched references. METHODS: Cohort study using prospectively collected healthcare data from the Skåne region, Sweden (~1.4 million residents). We extracted diagnoses for OA and 67 common chronic conditions. We included individuals aged 40+ years on 31 December 2007, with incident OA between 2008 and 2009. We selected references without OA, matched on birth year, sex, and year of death or moving outside the region. We employed group-based trajectory modelling to capture morbidity count trajectories from 1998 to 2019. Individuals without any comorbidity were included as a reference group but were not included in the model. RESULTS: We identified 9846 OA cases (mean age: 65.9 (SD 11.7), female: 58%) and 9846 matched references. Among both cases and references, 1296 individuals did not develop chronic conditions (no-chronic-condition class). We identified four classes. At the study outset, all classes exhibited a low average number of chronic conditions (≤1). Class 1 had the slowest progression towards multimorbidity, which increased progressively in each class. Class 1 had the lowest count of chronic conditions at the end of the follow-up (mean: 2.9 (SD 1.7)), while class 4 had the highest (9.6 (2.6)). The presence of OA was associated with a 1.29 (1.12, 1.48) adjusted relative risk of belonging to class 1 up to 2.45 (2.12, 2.83) for class 4. CONCLUSIONS: Our findings suggest that individuals with OA face an almost threefold higher risk of developing severe multimorbidity.

The performance of a Bayesian value-based sequential clinical trial design in the presence of an equivocal cost-effectiveness signal: evidence from the HERO trial.

BACKGROUND: There is increasing interest in the capacity of adaptive designs to improve the efficiency of clinical trials. However, relatively little work has investigated how economic considerations - including the costs of the trial - might inform the design and conduct of adaptive clinical trials. METHODS: We apply a recently published Bayesian model of a value-based sequential clinical trial to data from the 'Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis' (HERO) trial. Using parameters estimated from the trial data, including the cost of running the trial, and using multiple imputation to estimate the accumulating cost-effectiveness signal in the presence of missing data, we assess when the trial would have stopped had the value-based model been used. We used re-sampling methods to compare the design's operating characteristics with those of a conventional fixed length design. RESULTS: In contrast to the findings of the only other published retrospective application of this model, the equivocal nature of the cost-effectiveness signal from the HERO trial means that the design would have stopped the trial close to, or at, its maximum planned sample size, with limited additional value delivered via savings in research expenditure. CONCLUSION: Evidence from the two retrospective applications of this design suggests that, when the cost-effectiveness signal in a clinical trial is unambiguous, the Bayesian value-adaptive design can stop the trial before it reaches its maximum sample size, potentially saving research costs when compared with the alternative fixed sample size design. However, when the cost-effectiveness signal is equivocal, the design is expected to run to, or close to, the maximum sample size and deliver limited savings in research costs.

Non-coding RNAs as regulators of autophagy in chondrocytes: Mechanisms and implications for osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA.

The dynamic progression of temporomandibular joint osteoarthritis-like lesions elicited by mandibular shift in a rat model.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) presents significant challenges due to its complex etiology, often insidious onset, high incidence, and progressive structural deterioration. While research has explored genetic and molecular factors, treatment outcomes remain suboptimal, emphasizing the need for a deeper understanding of disease progression. OBJECTIVE: This study employs a specific mandibular shift rat model to explore the dynamic progression of TMJ-OA-like lesions and evaluate the potential for self-repair at different stages, aiming to inform early diagnosis and preventative strategies. METHODS: Seventy-two female Sprague-Dawley rats were randomized into three groups: a control group (n=24; average weight: 157.23±1.63 g) receiving sham surgery. an experimental group (n=24; average weight: 157.78±1.88 g) subjected to mandibular shift induction, and a removal group (n=24; average weight: 158.11±2.20 g) experiencing mandibular shift for one, two, or four weeks followed by a one-month recovery period (designated as 1w Removal, 2w Removal and 4w Removal, respectively). Histomorphological and molecular analyses were conducted at designated time points. RESULTS: Rats in the 1-week removal group exhibited substantial recovery in condylar morphology, cartilage thickness, extracellular matrix composition, and expression of OA-related genes. Conversely, the 4-week removal group mirrored the experimental group, indicating limited self-repair capacity at later stages. The 2-week removal group presented with variable outcomes, with some animals showing signs of recovery and others resembling the experimental group, indicating a potential transitional phase in the disease process. CONCLUSION: Recovery from early-stage TMJ-OA involves eliminating provoking factors such as occlusal interference or reducing joint loading. However, advanced stages exhibit diminished self-repair capabilities, necessitating additional therapeutic interventions. These findings emphasize the importance of early diagnosis and intervention in TMJ-OA management.

ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis.

Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Likely owing to the unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific ER proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the easily expandable cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.

Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes chondrogenesis in osteoarthritis.

BACKGROUND: Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. OBJECTIVE: We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes. METHODS: Chondrocytes were treated with interleukin (IL)-1ß to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay. RESULTS: CircTRIM25 was upregulated in OA tissues and IL-1ß-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1ß-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury in vivo. CONCLUSION: Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.

PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function.

Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.

IRF1 regulation of ZBP1 links mitochondrial DNA and chondrocyte damage in osteoarthritis.

BACKGROUND: Z-DNA binding protein 1 (ZBP1) is a nucleic acid sensor that is involved in multiple inflammatory diseases, but whether and how it contributes to osteoarthritis (OA) are unclear. METHODS: Cartilage tissues were harvested from patients with OA and a murine model of OA to evaluate ZBP1 expression. Subsequently, the functional role and mechanism of ZBP1 were examined in primary chondrocytes, and the role of ZBP1 in OA was explored in mouse models. RESULTS: We showed the upregulation of ZBP1 in articular cartilage originating from OA patients and mice with OA after destabilization of the medial meniscus (DMM) surgery. Specifically, knockdown of ZBP1 alleviated chondrocyte damage and protected mice from DMM-induced OA. Mechanistically, tumor necrosis factor alpha induced ZBP1 overexpression in an interferon regulatory factor 1 (IRF1)-dependent manner and elicited the activation of ZBP1 via mitochondrial DNA (mtDNA) release and ZBP1 binding. The upregulated and activated ZBP1 could interact with receptor-interacting protein kinase 1 and activate the transforming growth factor-beta-activated kinase 1-NF-κB signaling pathway, which led to chondrocyte inflammation and extracellular matrix degradation. Moreover, inhibition of the mtDNA-IRF1-ZBP1 axis with Cyclosporine A, a blocker of mtDNA release, could delay the progression of DMM-induced OA. CONCLUSIONS: Our data revealed the pathological role of the mtDNA-IRF1-ZBP1 axis in OA chondrocytes, suggesting that inhibition of this axis could be a viable therapeutic approach for OA.

Shoulder osteoarthritis: A survey of current (2024) UK physiotherapy practice.

BACKGROUND: Shoulder osteoarthritis can cause significant pain and disability. It is thought that the wider principles of osteoarthritis management can be applied in the management of people with shoulder osteoarthritis, but most prior research has been conducted with people experiencing osteoarthritis of the hip and knee. There is a paucity of evidence to guide the non-surgical management of shoulder osteoarthritis and limited understanding of current physiotherapy practice. OBJECTIVE: We aimed to investigate the current treatment recommendations by physiotherapists in the UK for people with shoulder OA. METHODS: An online survey using a clinical vignette was designed and distributed to UK registered physiotherapists with experience of managing people with shoulder osteoarthritis, via social media and professional networks. Descriptive statistics were used to analyse demographic and multiple-choice questions, and free text responses were summarised narratively. RESULTS: 114 respondents accessed the survey with 110 valid responses; 105 (95%) respondents would offer face-to-face consultations, with 89 (81%) respondents expecting to offer 2-4 appointments. 108 (98%) respondents would offer advice/education; 79 (72%) would offer weight management; 82 (75%) prescribed exercises to improve movement; and 101 (92%) offered exercises to increase strength. If a person lived with obesity or had a treatment preference, the majority of respondents would change their recommendations. CONCLUSION: This is the first survey of NHS physiotherapy practice for people with shoulder osteoarthritis. The responses largely align with NICE guidelines; despite this alignment, it is not known whether such guideline-based care is acceptable to people with shoulder osteoarthritis or clinically effective.

Cinnamaldehyde-Treated Bone Marrow Mesenchymal-Stem-Cell-Derived Exosomes via Aqueous Two-Phase System Attenuate IL-1ß-Induced Inflammation and Catabolism via Modulation of Proinflammatory Signaling Pathways.

Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1ß (IL-1ß) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1ß on chondrocytes. We stimulated chondrocytes with IL-1ß to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1ß on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-κB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1ß on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.