Cause Of Joint Pain Research Articles

Pediatric Orthopedic Emergencies

Proper care of orthopedic injuries and emergencies in children and adolescents requires knowledge of the altered bone and ligament characteristics, varying stages of skeletal development, and potential for congenital or developmental abnormalities. Pediatric fractures affecting the growth plate require unique management to maintain optimal growth. Whereas some specific fractures in these skeletally immature patients require urgent surgical repair, other fractures remodel extremely well and can be managed with a simple splint. Particular dislocations are common in this population and may have concomitant fractures. There are several overuse injuries seen primarily in children, and treatment aims to keep the patient active while allowing the injury to heal. Potentially devastating osteoarticular infections occur in the pediatric population and must be differentiated from more benign causes of joint pain, such as transient synovitis or congenital abnormalities. Children are also at risk for abnormalities such as slipped capital femoral epiphysis or Legg-Calvé-Perthes disease, which are rarely diagnosed in the adult population. It is imperative for a clinician to be aware of these and other nuances to optimally care for orthopedic injuries and emergencies in the pediatric population. This review contains 9 figures, 13 tables and 45 references Key words: bone, musculoskeletal, orthopedic, skeletal

Global Research Trends in Post-Traumatic Osteoarthritis: A Bibliometric and Visualized Study

Aim: Post-Traumatic osteoarthritis (PTOA) is a prevalent cause of joint pain and limited movement, significantly lowering people's quality of life. In recent years, with the increase of traffic accidents and accidental injuries, the incidence of articular cartilage injury has increased, and the incidence of traumatic arthritis has greatly increased. This research aims to look into the current worldwide status and trends in this subject. Method: On the Science Citation Index-Expanded Web of Science, the publications about PTOA were searched from 1994 to 2021. The data sources were studied and indexed by the method of bibliometrics. The data sources were studied and indexed by bibliometrics. To visualise, VOS viewer and GraphPadPrism7 software conducted bibliographic coupling analysis, co-authorship analysis, co-citation analysis, co-occurrence analysis, and the analysis of publication trends in PTOA research. Result: A total of 2239 related publications were collected. Globally, the number of papers published each year and the relative research interests are increasing. The cumulative published number of PTOA research accords with Logistic growth model: f(x) =a/(1+eb-cx). The United States contributes the most to worldwide research, receives the most citations, has the highest H index, and has the highest total link strength(TLS). Most papers have been published in the journal Osteoarthritis and Cartilage. The University of Calgary is the institution that makes the greatest contribution. Studies can be divided into four clusters: Mechanism Research, Tissue Engineering, Clinical Study, and Epidemiology. The investment in clinical research is relatively small. Conclusion: The number of publications on PTOA is expected to rise in the coming years, based on current global trends. In this field, the USA Is the biggest contributor. Noteworthy are the latest hot spots, including "Inflammation", "Anterior Cruciate Ligament Reconstruction", "Mesenchymal Stem Cell" and "differentiation". Therefore, there will be more and more studies on the mechanism of PTOA, which may inspire new clinical treatments for osteoarthritis caused by trauma.

Osteoartrose do joelho e corrida recreativa: uma revisão baseada na evidência

Osteoarthritis is a major cause of joint pain and disability, with the knee joint being the most commonly affected. The aim of this study is to investigate the evidence about the possible association between recreational running and the development of this pathology which is still controversial and sparse. Of the 409 articles in the initial research, four were included in this review. It was concluded that recreational running does not predispose to the development of clinical or radiographic knee osteoarthrosis, on the contrary, it seems to have a protective effect.

Osteoarthritis in Pseudoxanthoma Elasticum Patients: An Explorative Imaging Study.

Pseudoxanthoma elasticum (PXE) is a systemic disease affecting the skin, eyes, and cardiovascular system of patients. Cardiovascular disease is associated with osteoarthritis (OA), which is the most common cause of joint pain. There is a lack of systematic investigations on joint manifestations in PXE in the literature. In this explorative study, we aimed to investigate whether patients with PXE are more at risk for developing osseous signs of OA. Patients with PXE and hospital controls with whole-body low-dose CT examinations available were included. OA was assessed using the OsteoArthritis Computed Tomography (OACT)-score, which is a 4-point Likert scale, in the acromioclavicular (AC), glenohumeral (GH), facet, hip, knee, and ankle joints. Additionally, intervertebral disc degeneration was scored. Data were analyzed using ordinal logistic regression adjusted for age, body mass index (BMI), and smoking status. In total, 106 PXE patients (age 56 (48–64), 42% males, BMI 25.3 (22.7–28.2)) and 87 hospital controls (age 55 (43–67), 46% males, BMI 26.0 (22.5–29.2)) were included. PXE patients were more likely to have a higher OA score for the AC joints (OR 2.00 (1.12–3.61)), tibiofemoral joint (OR 2.63 (1.40–5.07)), and patellofemoral joint (2.22 (1.18–4.24)). For the other joints, the prevalence and severity of OA did not differ significantly. This study suggests that patients with PXE are more likely to have structural OA of the knee and AC joints, which needs clinical confirmation in larger groups and further investigation into the mechanism.

Reduction in Osteoarthritis Risk After Treatment With Ticagrelor Compared to Clopidogrel: A Propensity Score-Matching Analysis.

Osteoarthritis (OA) is a common cause of joint pain and disability, and effective treatments are lacking. Extracellular adenosine has antiinflammatory effects and can prevent and treat OA in animal models. Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine levels. This study was undertaken to determine whether treatment with ticagrelor was associated with a lower risk of OA. We conducted a 1:2 propensity score-matching analysis using data from 2011-2017 in the Optum Clinformatics Data Mart. Patients who had received either ticagrelor or clopidogrel for ≥90 days were included in our study, and patients with a prior diagnosis of OA or inflammatory arthritis were excluded. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor versus clopidogrel. Our propensity score-matched cohort consisted of 7,007 ticagrelor-treated patients and 14,014 clopidogrel-treated patients, with a median number of days receiving treatment of 287 and 284, respectively. For both groups, the mean age was 64 years, and 73% of the patients were male. Multivariate Cox regression analysis estimated a hazard ratio for developing OA of 0.71 (95% confidence interval 0.64-0.79) (P < 0.001) after treatment with ticagrelor compared to clopidogrel. Treatment with ticagrelor was associated with a 29% lower risk of developing OA compared to treatment with clopidogrel over 5 years of follow-up. We hypothesize that the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine levels.

Mesenchymal Stem Cells Derived from Synovium and Fat Pad are Able to Treat Induced Ankle Osteoarthritis in Rats?

Category:Ankle Arthritis; Ankle; Basic Sciences/BiologicsIntroduction/Purpose:Osteoarthritis (OA) is a chronic disease and a significant cause of joint pain, tenderness, and limitation of motion. At present, no specific treatment is available and mesenchymal stem cells (MSCs) have shown promising potentials in this regard. Herein, we aimed to evaluate the repairing potentials of stem cells derived from synovium and fat pad in treatment of OA in ankle joint.Methods:Twenty-eight male rats (220+-20 g, aged 10-12 weeks), were randomly divided into four groups (n=7): C1: non- treated, C2: Hyalgan treated, E1: Adipose-tissue derived stem cell treated, and E2: synovial-membrane based stem cell treated groups. Collagenase type II enzyme was injected into the left ankle; after eight weeks, OA was developed. Then, stem cells were injected and rats were followed for three months. Afterwards, rats were euthanized and specimens and radiological images were provided. P-value<=0.05 was set as statistically significant.Results:Compared to C1, E1 and E2 groups showed significantly better results in all pathological criteria including surface, matrix, cell distribution, cell population viability, subchondral bone, and cartilage mineralization as well as joint space width and osteophytes developed in the joint (p<=0.001). Similarly, compared to C2 group, E1 and E2 had better scores regarding surface, matrix, cell distribution, and cell population viability (p<0.05). E2 showed considerably higher scores compared to C2 regarding subchondral bone and cartilage mineralization (p<0.05). Joint space width was similar between C2 and E groups.Conclusion:Treatment of OA of ankle with MSCs, particularly synovial-membrane derived stem cells, not only prevented but also healed OA to some extent in comparison to Hyalgan and non-treatment groups.

Overview of Juvenile Idiopathic Arthritis

Joint pain is a common symptom in children and adolescents. While there are many causes of joint pain in children, most of these are acute or not related to underlying joint inflammation. Chronic arthritis, however, can be one of the reasons behind the joint pain. The most common causes of chronic arthritis in children are categorized under juvenile idiopathic arthritis (JIA). The purpose of this review is to highlight the most important clinical features, work-up, and medical management of the different subtypes of JIA.

Gene Expression Profiling Studies Using Microarray in Osteoarthritis: Genes in Common and Different Conditions.

Osteoarthritis (OA), which is characterized mainly by cartilage degradation, is the most prevalent joint disorder worldwide. Although OA is identified as a major cause of joint pain, disability, and socioeconomic burden, the etiology of OA is still not clearly known. Recently, gene microarray analysis has become an efficient method for the research of complex diseases and has been employed to determine what genes and pathways are involved in the pathological process of OA. In this review, OA study results over the last decade are summarized for gene expression profiling of various tissues, such as cartilage, subchondral bone, and synovium in human OA and mouse OA models. Many differentially expressed genes, which mainly involve matrix metabolism, bone turnover, and inflammation pathways, were identified in diseased compared with "normal" tissues. Nevertheless, rare common genes were reported from studies using different tissue sources, microarray chips, and research designs. Thus, future novel and carefully designed microarray studies are required to elucidate underlying genetic mechanisms in the pathogenesis of OA as well as new directions for potential OA-targeted pharmaceutical therapies.

Pigmented Villonodular Synovitis Mimicking an Acute Septic Hip in an Eight-Year-Old Male

Pigmented villonodular synovitis (PVNS) is a less common but known cause of joint pain in the adult population. PVNS in pediatric patients is even more rare, with only case reports of occurrence in persons under the age of 18 years. Presentation is typically that of more insidious pain and limited range of motion, and is primarily seen in the knee joint. Diagnosis can be suspected with imaging, but ultimately surgical intervention is needed for tissue confirmation. We present a case of PVNS in a pediatric patient with acute symptoms concerning for a septic joint. The patient’s workup revealed a large effusion on hip ultrasound, with operative intervention pursued and further imaging deferred given the patient's symptom burden. A 4 × 1 × 1.5 cm intra-articular pigmented mass excised from the synovium in the operating room. The patient’s symptoms improved after the procedure, with pathology showing sheets of plump mononuclear cells in a collagenized stroma with hemosiderin deposits, confirming the diagnosis. This case highlights the importance of keeping non-infectious etiologies in the differential diagnosis of acute onset joint pain.

Telomere shortening is associated with poor physical performance in knee osteoarthritis.

Telomere length is a hallmark characteristic of ageing and age-related diseases. Osteoarthritis (OA) is the most common cause of joint pain and physical disability in the elderly. Previous studies have revealed the role of telomere shortening in OA; however, the relationship between telomere length, muscle strength and physical performance in knee OA patients remains unknown. The aim of the present study was to investigate the association of telomere length and physical performance in patients with knee OA. A total of 202 patients with knee OA and 60 healthy controls were enrolled in the study. The quality of life was assessed using Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Short Form Health Survey. The skeletal muscle mass was examined using bioelectrical impedance analysis, while the muscle strength was analyzed using hand grip force and isometric knee extension force. The physical performance of patients with knee OA was also investigated using gait speed, Timed up and go test (TUGT), Sit to stand test and 6-min walk test (6MWT). Blood leukocyte relative telomere length (RTL) was assessed using real time quantitative PCR. The mean blood leukocyte RTL in knee OA subjects was significantly lower compared with healthy controls (P<0.001). Knee OA patients with RTL values in the lowest quartile had a slow gait speed (P=0.006) and prolonged TUGT time (P=0.03). Multivariate regression analyses and multiple logistic regression analyses adjusted for age, sex, waist circumference, body mass index, fat mass, skeletal muscle index and the total WOMAC demonstrated that gait speed, TUGT and 6MWT were associated with longer RTL (P-trend<0.05). These findings suggested that poorer physical performance was associated with shorter RTL. Therefore, leukocyte telomere length and physical performance tests, especially gait speed, TUGT and 6MWT, could predict the health status and quality of life in patients with knee OA.

Pain behaviour assessments by gait and weight bearing in surgically induced osteoarthritis and inflammatory arthritis

Objective. Osteoarthritis (OA) is the most common cause of joint pain. Animal models and relevant assays for measurement of pain-related behaviours are important tools for studies of mechanisms inducing and sustaining pain in OA. The aim of this study was to evaluate two different assessments of weight bearing; stationary and during locomotion, and to explore their feasibility to detect analgesic effects in vivo. Two fundamentally different mouse models of joint arthritis were investigated; surgical transection of the anterior cruciate ligament (ACLT) resulting in destabilization of the joint with subsequent structural deterioration resembling OA, and monoarthritis induced by injection of Complete Freund´s Adjuvant (CFA) into the ankle joint capsule. Design. Mice were subjected to ACLT or CFA injection into the ankle joint. Stationary weight bearing was performed up to twenty weeks after ACLT, and for two weeks after CFA. In addition, mice with CFA-induced monoarthritis were assessed for gait and weight bearing during locomotion, and the effects of an anti-NGF antibody (MEDI578) were tested. End point histopathological analysis was performed in knee joints of ACLT mice, and in mice with ankle joint injection of CFA at eight days after injection. Results. Both the surgical ACLT and CFA-induced monoarthritis reduced stationary weight bearing on the affected paw. The reduction in weight bearing was compensated by all other legs, but differently when stationary compared to during locomotion in the CFA-injected mice. The behavioural effects of ACLT correlated to the structural changes of the joint. In the CFA-induced monoarthritis, showing a massive infiltration of inflammatory cells at 8 days, MEDI578 significantly attenuated the pain-like behaviours. Conclusions. The pain-like behaviour detected is mainly due to inflammation and not to the same degree to structural changes in the joint. Behavioural effects after ACLT were too small for pharmacological evaluation of pain relief. In contrast, the inflammation after CFA injection caused a long-lasting effect on pain-like behaviours such as weight bearing and gait, which could be attenuated by administration of an anti NGF antibody.

Are Stem Cells Derived from Synovium and Fat Pad Able to Treat Induced Knee Osteoarthritis in Rats?

Background Osteoarthritis (OA) is a chronic disease and a significant cause of joint pain, tenderness, and limitation of motion. At present, no specific treatment is available, and mesenchymal stem cells (MSCs) have shown promising potentials in this regard. Herein, we aimed to evaluate the repairing potentials of stem cells derived from the synovium and fat pad in the treatment of OA. Methods Twenty-eight male rats (220 ± 20 g, aged 10-12 weeks), were randomly divided into four groups (n = 7): C1: nontreated group, C2: Hyalgan-treated group, E1: adipose tissue-derived stem cell-treated group, and E2: synovial membrane-based stem cell-treated group. Collagenase type II was injected into the left knee; after eight weeks, OA was developed. Then, stem cells were injected, and rats were followed for three months. Afterward, specimens and radiological images were investigated. p value ≤ 0.05 was set as statistically significant. Results Compared to the C1 group, the E1 and E2 groups showed significantly better results in all six pathological criteria as well as joint space width and osteophytes of medial tibial, medial femoral, and medial fabellar condyles (p ≤ 0.001). Similarly, compared to the C2 group, the E1 and E2 groups had better scores regarding surface, matrix, cell distribution, and cell population viability (p < 0.05). E2 showed considerably higher scores compared to C2 regarding subchondral bone and cartilage mineralization (p < 0.05). The joint space width was similar between the C2 and E groups. Conclusion Treatment of OA with MSCs, particularly synovial membrane-derived stem cells, not only prevented but also healed OA of the knee to some extent in comparison to the Hyalgan and nontreatment groups.

Immunoregulatory Effects of Krocina™, a Herbal Medicine Made of Crocin, on Osteoarthritis Patients: A Successful Clinical Trial in Iran.

Osteoarthritis (OA) is the major cause of joint pain and disability. This research was planned to examine the effects of Krocina™, aherbal medicine made of crocin, an ingredient of saffron, in patients with OA. Forty patients suffering from OA were enrolled in our study and randomly divided into two groups, receiving Krocina™ and placebo, and the clinical trial continued for four months.Peripheral blood was taken from all patients and the percentage ofvarious subsets of T cells in addition to the levels of forkhead box protein P3 (FOXP3) and interleukin (IL)-17 were measured by flow cytometry technique. The visualan alog scale (VAS) index analysis decreased significantly in both groups (krocinaTM and placebo) (p<0.05). Assessment of the C-reactive protein (CRP) level in serum showed a significant decrease in the krocinaTM group (p<0.05). Moreover, we found a meaningful increase in the percentage of regulatory T cells (Tregs)cellin samples gathered from Krocina™ group (P=0.02) patients. The mean percentages of T helper (Th) 17 cellsinthe Krocina™ group and CD8+ T cellsin the placebo group patients were also meaningfully reduced (p<0.05). The geometric mean fluorescence intensity (GMFI) for IL-17 showed a significant decrease and increase in Krocina™ and placebo groups, respectively (p<0.05). No noticeable difference was observed in the percentages of Th cells and GMFI-FOXP3 in either group. Treg/Th17 ratio was shifted towards Tregscell in Krocina™ group at the end of the intervention. It is concluded that Krocina™ has immunoregulatory effects on patients with OA, ameliorating the disease.

Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models.

Osteoarthritis (OA) is a chronic degenerative joint disease and the major cause of joint pain and disability in the elderly. It is mainly characterized by articular cartilage degradation and subchondral bone remodeling. There are two main types of OA: natural occurring OA and secondary OA, mainly associated with aging and trauma, respectively. In this study, we established two OA models in rat knee joints to simulate the two types of OA, using the type II collagenase injection (CI) and anterior cruciate ligament transection (ACLT), respectively. After intervention for 2–6 weeks, cartilage and subchondral bone changes were detected in histological staining, immunochemistry, and micro-CT. Results showed that both models with typical pathology changes of OA were successfully induced, while the development and severity of OA process in the models were different. In ACLT rats, the cartilage damage was milder, lasted for a shorter time, and subchondral bone reconstruction occurred earlier, compared with the changes in CI rats. The cartilage damage was secondary to subchondral bone change in ACLT rats, while subchondral bone change was secondary to cartilage degeneration in CI rats. In conclusion, the interaction between cartilage and subchondral bone is different between the natural-occurring and secondary OA models. These two models not only suggest potential different mechanisms of the two types of OA, but also provide new directions for OA treatment and prevention.

Osteoarthritis as an inflammatory disease

Osteoarthritis (OA) is the most common joint disease worldwide and is a major ca use of joint pain and disability. Traditionally OA was considered primarily as a disease determined by progressive articular cartilage breakdown, caused by exposure to different mechanical and biological factors. The contemporary concept of OA emphasizes the complex pathogenesis of the disease, as a disorder of the joint as a whole organ, which involves not only hyaline cartilage, but also underlying bone and synovial tissue (synovium). Histological examination of synovial membrane have shown in most OA patients, infiltration of inflammatory cells into the synovium (synovitis), thickening of the synovium, increased production of pro-inflammatory cytokines. Significant inflammatory changes might be observed in the synovium even before evident cartilage damage occurs, however synovitis is present in all stages of OA. The histopathological and molecular examinations a well as modern imaging modalities (magnetic resonance, ultrasound) support the relevance of synovitis in OA. Synovial inflammation seems to be pivotal in the pathogenesis of OA, it is significantly associated with clinical symptoms (pain, morning stiffness), impairment of physical function. Synovitis could be an independent risk factor indicating progressive structural damage of OA and associated radiological changes. The goal of OA therapy is the reduction of pain and at least in some patients it is achie ved with anti-inflammatory treatment, using non-steroidal anti-inflammatory drugs (NSAIDs) or intra-articular glucocorticosteroid injections. The research of other treatment is in progress, looking for therapeutics of long-term anti-inflammatory effect, inhibiting the low-grade inflammation and the progress of degenerative change.

Ultrasound guided intra-articular botulinum toxin injection for treatment of the osteoarthritic knee pain: expert opinion.

Osteoarthritis is the most common form of arthritis and cause of joint pain and disability [1]. The prevalence, burden and socioeconomic impact of osteoarthritis of the knee is considerable and growing [2]. Knee pain is the most cardinal symptom of the osteoarthritic knee and is associated with a high degree of impaired function and daily activities [3]. Intra-articular injection provides a safe and cost effective control of knee pain with improvement of function and activities of daily living [4]. Ultrasound guidance improves the accuracy of the intra-articular injection in knee joint and clinical outcomes and lowers health care costs [5]. Botulinum toxin targets many neuropeptides leading to reduction of pain, peripheral sensitization and in turn reduction of the central sensitization. Also, botulinum toxin plays an anti-inflammatory role by reduction of the neurogenic inflammation [6]. The following table summarizes how to use botulinum toxin in clinical practice according to authors experience. However, further large-scale multicenter randomized controlled trials are needed to confirm effectiveness and determine the exact position of this intervention in the therapeutic armamentarium for the osteoarthritic knee pain.

Use of Magnetic Resonance Imaging to Identify Immune Checkpoint Inhibitor–Induced Inflammatory Arthritis

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for an ever-increasing number of cancers. However, their use has also led to the emergence of immune-related adverse events, such as ICI-induced inflammatory arthritis. A reproducible, reliable, and accessible modality is needed to assess and distinguish early ICI-induced inflammatory arthritis and help in management. Magnetic resonance imaging (MRI) of joints may be helpful for early diagnosis, guiding therapeutic decision-making, and identifying patients at high risk for erosive disease. To assess the role of MRI of joints in patients with ICI-induced inflammatory arthritis. This retrospective case series included patients enrolled at the National Institutes of Health Clinical Center in Bethesda, Maryland. Patients were evaluated by the rheumatology consultation service between December 27, 2016, and May 28, 2019. A retrospective health record review was performed to determine demographic characteristics, clinical characteristics of inflammatory arthritis and malignant tumors, and imaging findings. Inclusion criteria were patients who were enrolled on various institutional review board-approved protocols of ICIs, developed joint-related symptoms, and had MRI data for at least 1 joint. Data were analyzed from June 1, 2019, to September 1, 2019. Undergoing MRI of at least 1 joint. All MRIs were reviewed for synovitis, tenosynovitis, bone marrow edema, and soft tissue conditions. A total of 8 patients (mean [SD] age, 58.8 [5.2] years; 6 women and 2 men) between the ages of 50 and 65 years who were undergoing ICI therapy for a variety of malignant tumors were included in this study. Only 1 patient was receiving combined ICI therapy. The results of 13 separate MRI examinations were reviewed. The most commonly performed MRIs were of the hands and wrists (9 MRIs), followed by knee examinations (3 MRIs). Tenosynovitis and synovitis were frequently seen in the hands and wrists. Bone marrow edema and erosions were also found in 3 patients, suggesting early damage. In larger joints (ie, knees and ankles), joint effusions and synovial thickening were characteristic. Most patients (5 patients) were treated with corticosteroids and had good responses. In patients with high-risk features on MRI imaging (eg, bone marrow edema, erosions), disease-modifying antirheumatic drug therapy was also discussed as a treatment option. These findings suggest that advanced imaging may help to distinguish ICI-induced inflammatory arthritis from other causes of joint pain, aid in identifying patients at increased risk of joint damage, and provide utility in monitoring inflammatory arthritis treatment response in patients receiving ICI therapy.

Attenuation of IL-1ß on the use of glucosamine as an adjuvant in meloxicam treatment in rat models with osteoarthritis.

Background Osteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. The severity of this disease is always associated with increased levels of proinflammatory cytokines, which play an important role in cartilage damage, synovitis, and other damage to joint tissues. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory state. Several studies show that cytokines, such as interleukin 1ß, have a major role in the development of inflammation that occurs in these joints. The use of glucosamine as an adjuvant to meloxicam therapy is expected to inhibit the development of inflammatory OA. Methods The OA model in rat was induced by single injection of intraarticular monosodium iodoacetate (MIA). The development of OA was observed for 21 days. Furthermore, the evaluation of glucosamine potency as an adjuvant of meloxicam therapy for reducing IL-1ß was done by combined treatment at a low dose of meloxicam 1 mg/kg BW with glucosamine at a dose of 125, 250, or 500 mg/kg BW orally for 28 days. Response to hyperalgesia and knee joint diameter was measured on days 0, 7, 14, 21, 28, 35, 42, and 49. IL-1ß levels were measured on day 21 and day 49 after MIA injection. Results MIA injection successfully induced OA as marked by a significant difference in the time of latency to heat stimulus (p < 0.01) and a significant increase in joint diameter (p < 0.01). On day 21, IL-1ß levels showed a significant decrease in MIA injection (p = 0.05). The administration of meloxicam and glucosamine did not induce significant decrease in knee joint diameter (p > 0.10), but was able to significantly increase the latency time to heat stimulus (p < 0.01). IL-1ß levels also showed a significant decrease after administering a combination of glucosamine and meloxicam (p < 0.01). Conclusions Taken together, the use of glucosamine as an adjuvant in meloxicam therapy may be caused by the synergistic mechanism of meloxicam for the attenuation of OA development through systemically reducing IL-1ß.

MiR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence

Osteoarthritis (OA) is a major cause of joint pain and disability, and chondrocyte senescence is a key pathological process in OA and may be a target of new therapeutics. MicroRNA-140 (miR-140) plays a protective role in OA, but little is known about its epigenetic effect on chondrocyte senescence. In this study, we first validated the features of chondrocyte senescence characterized by increased cell cycle arrest in the G0/G1 phase and the expression of senescence-associated β-galactosidase (SA-βGal), p16INK4a, p21, p53, and γH2AX in human knee OA. Then, we revealed in interleukin 1β (IL-1β)-induced OA chondrocytes in vitro that pretransfection with miR-140 effectively inhibited the expression of SA-βGal, p16INK4a, p21, p53, and γH2AX. Furthermore, in vivo results from trauma-induced early-stage OA rats showed that intra-articularly injected miR-140 could rapidly reach the chondrocyte cytoplasm and induce molecular changes similar to the in vitro results, resulting in a noticeable alleviation of OA progression. Finally, bioinformatics analysis predicted the potential targets of miR-140 and a mechanistic network by which miR-140 regulates chondrocyte senescence. Collectively, miR-140 can effectively attenuate the progression of early-stage OA by retarding chondrocyte senescence, contributing new evidence of the involvement of miR-mediated epigenetic regulation of chondrocyte senescence in OA pathogenesis.

Fibulin-3 serum and urine levels in the diagnosis and severity assessment of primary knee osteoarthritis.

ObjectivesOsteoarthritis (OA) is the most widespread joint disease and is a major cause of joint pain and disability in the middle aged and elderly population. The diagnosis of OA is based on clinical and radiographic changes that occur late after disease progression, and hence does not allow early detection of structural damage. Therefore, there is an acute need for reliable biochemical markers that can facilitate its earlier diagnosis. This study was commenced to identify fibulin-3 levels in serum and urine of patients with primary knee OA and to investigate their relationship with severity of the disease.Material and methodsFifty female patients with primary knee OA were compared to 25 healthy female controls. Fibulin-3 in serum and urine were measured using enzyme-linked immunosorbent assay (ELISA). Severity of knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the Knee Outcome Survey Activities of Daily Living (KOS-ADL) scale. Radiographic grading of knee OA was performed by Kellgren-Lawrence (K-L) criteria.ResultsSerum and urine fibulin-3 were higher in patients (286.00 ±145.00 ng/ml and 104.60 ±32.73 ng/ml, respectively) than in controls (26.00 ±5.77 ng/ml and 13.60 ±4.21 ng/ml, respectively). Fibulin-3 in serum and urine correlated (p < 0.001) with each other (r = 0.930) and with the severity of knee pain by WOMAC index (r = 0.909 and 0.928, respectively), inversely correlated with KOS-ADL (r = –0.913 and –0.953, respectively), and with radiographic grading of K-L (r = 0.855 and 0.875, respectively).ConclusionsFibulin-3 serves as a biomarker of knee OA disease severity and could predict disease progression. Assessing urine fibulin-3 could be an applicable and easy method to diagnose knee OA and to follow up disease progression.