Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
29384051 Current Status of Molecular Imaging in Inflammatory and Autoimmune Disorders. 2018 In the field of inflammation imaging, nuclear medicine techniques can be considered as a non-invasive tool to early detect pathophysiological changes in affected tissues. These changes usually occur before clinical onset of symptoms and before the development of anatomical changes, that are commonly detected by radiological procedures. This is particularly important for prognostic purposes, therapy decision making and for therapy follow-up. Here we review the current state-of-the art of nuclear medicine for diagnostic purposes in different conditions characterized by a chronic inflammation, such as vulnerable atherosclerotic plaques, vasculitis, rheumatoid arthritis, Sjogren syndrome, autoimmune thyroid diseases, inflammatory bowel diseases, Coeliac disease, Type 1 diabetes mellitus and other immunological diseases. Overall, we describe several different approaches based on radiolabeled cells, peptides and antibodies or FDG. It emerges the role of PET and of hybrid cameras in particular (SPECT/CT and PET/CT) for diagnosis of these disorders and for therapy decision making and followup.
29344005 Biological clocks: their relevance to immune-allergic diseases. 2018 The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made in the past 15 years on the genetic and molecular mechanisms regulating many physiological functions, has renewed the attention to the importance of circadian rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus in the brain, photoentrained via direct connection with melanopsin containing, intrinsically light-sensitive retinal ganglion cells, and it projects to periphery, thus creating an inner circadian rhythm. This regulates several activities, including sleep, feeding times, energy metabolism, endocrine and immune functions. Disturbances of these rhythms, mainly of wake/sleep, hormonal secretion and feeding, cause decrease in quality of life, as well as being involved in development of obesity, metabolic syndrome and neuropsychiatric disorders. Most immunological functions, from leukocyte numbers, activity and cytokine secretion undergo circadian variations, which might affect susceptibility to infections. The intensity of symptoms and disease severity show a 24 h pattern in many immunological and allergic diseases, including rheumatoid arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is accompanied by altered sleep duration and quality, a major determinant of quality of life. Shift work and travel through time zones as well as artificial light pose new health threats by disrupting the circadian rhythms. Finally, the field of chronopharmacology uses these concepts for delivering drugs in synchrony with biological rhythms.
29308627 Semaphorin-3A as An Immune Modulator Is Suppressed by MicroRNA-145-5p. 2018 Apr OBJECTIVES: Semaphorin-3A (SEMA3A) and its receptors are found on some immune cells and act as suppressors of immune cells over-activation. Considering the role of SEMA3A and its down-regulation in some autoimmune diseases, as well as our bioinformatics predictions, we assumed that miR-145-5p might affect SEMA3A expression. So, we aimed to determine the effect of miR-145-5p on SEMA3A gene expression level. MATERIALS AND METHODS: In this experimental study, we evaluated the effect of miR-145-5p transfection on SEMA3A expression in peripheral blood mononuclear cells (PBMCs) using ELISA and quantitative real-time polymerase chain reaction (PCR) methods. RESULTS: Our results showed that miR-145-5p is able to decrease SEMA3A expression at both protein and mRNA levels. These data confirmed our previous bioinformatic prediction about the inhibitory effect of miR-145-5p on SEMA3A expression. CONCLUSIONS: These results enlightened us about an unknown aspect of SEMA3A role in some autoimmune disorders like multiple sclerosis (MS) and rheumatoid arthritis (RA) and also proposed SEMA3A as a potential therapeutic approach.
29136797 Unparalleled sample treatment throughput for proteomics workflows relying on ultrasonic en 2018 Feb 1 We report on the new microplate horn ultrasonic device as a powerful tool to speed proteomics workflows with unparalleled throughput. 96 complex proteomes were digested at the same time in 4min. Variables such as ultrasonication time, ultrasonication amplitude, and protein to enzyme ratio were optimized. The "classic" method relying on overnight protein digestion (12h) and the sonoreactor-based method were also employed for comparative purposes. We found the protein digestion efficiency homogeneously distributed in the entire microplate horn surface using the following conditions: 4min sonication time and 25% amplitude. Using this approach, patients with lymphoma and myeloma were classified using principal component analysis and a 2D gel-mass spectrometry based approach. Furthermore, we demonstrate the excellent performance by using MALDI-mass spectrometry based profiling as a fast way to classify patients with rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Finally, the speed and simplicity of this method were demonstrated by clustering 90 patients with knee osteoarthritis disease (30), with a prosthesis (30, control group) and healthy individuals (30) with no history of joint disease. Overall, the new approach allows profiling a disease in just one week while allows to match the minimalism rules as outlined by Halls.
29058773 The role of innate lymphoid cells in health and disease. 2018 Jun Innate lymphoid cells (ILCs) are kind of innate immune cells which can be divided into three main subsets according to their cytokine release profile, transcription factors, and surface markers. ILCs affect the initial stages of immunity in response to microbes and participate in immunity, inflammation, and tissue repair. ILCs modulate immunity through resistance to the pathogens and regulation of autoimmune inflammation and metabolic homeostasis. Therefore dysregulation of ILCs may lead to chronic pathologies such as allergies (i.e., asthma), inflammation (i.e., inflammatory bowel disease), and autoimmunity (i.e., psoriasis, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, and ankylosing spondylitis). Regarding the critical role of ILCs in the regulation of immune system, the elucidation of their function in different conditions makes an interesting target for improvement of novel therapeutic approach to modulate an immune response in different disease context.
29049037 Fractures and the gut microbiome. 2018 Jan PURPOSE OF REVIEW: The role of the gut microbiome in the pathogenesis of several inflammatory, non-AIDS comorbidities, such as cardiovascular disease, cognitive impairment and liver disease has become a focus of recent research. Low bone mineral density (BMD) and increased fracture incidence in people living with HIV (PLWH) is also widely reported, however, the relationship between alterations in the gut microbiome and bone disease in PLWH has not been previously reviewed. RECENT FINDINGS: Murine models that manipulate the gut microbiome, either through breeding of 'germ-free' mice or antibiotic-depleted gut microbiome, show differences in bone mineral density and bone mass in those with altered gut microbiome. This effect is reported to be driven via changes in the gut-immune-skeletal axis, with changes favouring bone resorption. Several inflammatory conditions wherever bone loss is a prominent feature, such as rheumatoid arthritis and inflammatory bowel disease, have also reported alterations in the gut microbiome, which are associated with bone loss, again through changes in the gut-immune-skeletal axis. SUMMARY: The interplay between the gut microbiome and the immune-skeletal axis in HIV represents a complex relationship. Alterations in the gut microbiome, which induce an activated immune phenotype and inflammatory milieu are associated with non-AIDS comorbidities in PLWH and bone loss in several other conditions characterized by chronic immune activation and inflammation. It is, therefore, likely that there are comparable effects between altered gut microbiome and bone loss in HIV, however, further research is required to better define this relationship in populations of PLWH.
28938865 Binding of ibuprofen to human hemoglobin: elucidation of their molecular recognition by sp 2018 Sep Ibuprofen, used for the treatment of acute and chronic pain, osteoarthritis, rheumatoid arthritis, and related conditions has ample affinity to globular proteins. Here we have explored this fundamental study pertaining to the interaction of ibuprofen with human hemoglobin (HHb), using multispectroscopic, calorimetric, and molecular modeling techniques to gain insights into molecular aspects of binding mechanism. Ibuprofen-induced graded decrease in absorption spectra indicates protein disruption along with sedimentation of HHb particle. Red shifting of absorption peak at 195 nm indicates alteration in the secondary structure of HHb upon interaction with ibuprofen. Flouremetric and isothermal titration calorimetric (ITC) studies suggested one binding site in HHb for ibuprofen at 298.15 K. However, with increase in temperature, ITC revealed increasing number of binding sites. The negative values of Gibbs energy change (ΔG(0)) and enthalpy change (ΔH(0)) along with positive value of entropy change (ΔS(0)) strongly suggest that it is entropy-driven spontaneous exothermic reaction. Moreover, hydrophobic interaction, hydrogen bonding, and π-π interaction play major role in this binding process as evidenced from ANS (8-anilino-1-napthalenesulphonic acid), sucrose binding, and molecular modeling studies. The interaction impacts on structural integrity and functional aspects of HHb as confirmed by CD spectroscopy, increased free iron release, increased rate of co-oxidation and decreased rate of esterase activity. These findings suggest us to conclude that ibuprofen upon interaction perturbs both structural and functional aspects of HHb.
28872680 Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte 2018 Jan OBJECTIVES: Many studies of disease state mechanisms reveal that unbridled inflammation is to blame for many of the symptoms associated with autoimmune diseases such as Crohn's and Rheumatoid Arthritis (RA). While therapies aimed at decreasing levels of pro-inflammatory cytokines exist, some have failed clinically or have extensive adverse effects. The aim of this review is to discuss common drug targets for anti-inflammatory therapies as well as explore potential mechanisms of action for new therapies. Various studies done on novel mechanisms targeting pro-inflammatory cytokine release as well as leukocyte chemotaxis have been researched for discussion here. Both of these contribute to tissue injury and patient symptoms in inflammatory and autoimmune disease states. KEY FINDINGS: While many current drug targets suppress inflammation via the receptor, research aimed at identifying new compounds and signaling mechanisms is ongoing to identify new targets within pro-inflammatory signaling pathways, or specific immune cell types. CONCLUSIONS: While glucocorticoids and monoclonal antibodies have shown to be efficacious, some patients have encountered mixed results. Biologic therapies also come with a high price tag Thus, novel compounds with new immune drug targets are ideal for patients whose therapies have not been successful.
30677879 Increased prevalence of Sjogren's syndrome in where soils contain high levels of chromium. 2019 Mar 20 Previously, we showed that farm soil levels of chromium were strongly correlated with people's serum chromium levels and an increase (3.6 fold) in both the incidence and prevalence of sicca syndrome in areas where farm soil chromium was high. Because Sjogren's syndrome (SS) is the major disease causing a dry mouth and dry eyes, we aimed in the study to investigate whether these areas with high soil chromium have a high SS prevalence. We used a database from the authority in charge of catastrophic illness certificates. Heavy metal concentrations in farm soils were retrieved from nationwide surveys. We used spatial regression models to study the relationships between the SS prevalence and soil metal concentrations. There were 11,220 people, 1165 men and 10,055 women who received a SS certificate from 2000 to 2011. The SS prevalence was 31 per 105 people, 5.59 for men and 55.01 for women. The highest SS prevalence in Taiwan (53 per 105) was located in an area where farm soils contain the highest amounts of chromium. In contrast, other types of heavy metal did not show such a strong association. In conclusion, the SS prevalence is significantly increased in areas where soils contain high levels of chromium. Chromium is likely a risk for SS.
30344882 Prevalence of inflammatory back pain and radiologic sacroiliitis is increased in patients 2018 INTRODUCTION: The prevalence of Sjögren's syndrome (SS) in patients with the diagnosis of SpA has been reported to be higher than normal population. Yet, the vice-versa is unclear. In this study, we aimed to investigate the prevalence of IBP, radiologic sacroiliitis and SpA in patients with primary SS. METHODS: 85 patients followed at the rheumatology clinics of the Marmara and Kocaeli Universities with the diagnosis of primary SS between November 2011 and August 2012 were included in this study. The control group consisted of 100 age-and gender-matched patients. Inflammatory back pain and axial SpA were diagnosed according to the assessment of spondylo arthritis International Society (ASAS) criteria. RESULTS: 83 patients were (97%) female and 2 (3%) were male. Mean age of the patients was 49.1 (±11) years. Mean disease duration was 7.3 (±4) years. The patient and control groups were comparable in terms of age and gender (p > 0.05). Inflammatory back pain was observed in 21 (24.7%) of 85 primary SS patients and in 4 (4%) of 100 control subjects (p < 0.001), radiographic sacroiliitis was demonstrated in 9 (10.5%) of primary SS patients and 2 (2%) of the control subjects (p = 0.025). Remaining SpA findings were not encountered in either group. CONCLUSION: inflammatory back pain and radiologic sacroiliitis is increased in patients with primary SS. Whether IBP, SI joint inflammation and radiologic sacroiliitis is due to the co-existence of SpA and primary SS or IBP is an underdiagnosed clinical feature of SS deserves further studies of large patient numbers.
30270699 Increased B-cell activating factor, interleukin-6, and interleukin-8 in induced sputum fro 2019 Mar OBJECTIVE: Small airway disease and chronic obstructive pulmonary disease are common in primary Sjögren's syndrome (pSS). However, the underlying inflammatory mechanisms behind pSS-associated airway disease have not been studied in detail. We therefore wanted to study cytokine and leucocyte levels in induced sputum in never-smoking patients with pSS. METHOD: Induced sputum cytokines and leucocytes were assessed in 20 never-smoking patients with pSS and 19 age- and gender-matched population-based controls. In addition, pulmonary function, disease activity, respiratory symptoms, and inflammatory and serological features of pSS were assessed. RESULTS: B-cell activating factor (BAFF), interleukin-6 (IL-6) and IL-8 were significantly increased in induced sputum in pSS patients compared to population-based controls, while IL-1β, interferon-α, and tumour necrosis factor-α levels and leucocytes were not. The proportion of lymphocytes and BAFF levels in induced sputum correlated significantly in pSS patients. However, cytokine levels in induced sputum were not associated with pulmonary function tests, disease activity, respiratory symptoms, or serological features of pSS. CONCLUSION: The increase in BAFF, IL-6, and IL-8 in induced sputum suggests a specific ongoing inflammatory disease process in the airways in pSS patients. Its association with pSS-associated airway disease needs to be further examined in future larger studies.
29934634 Meibomian gland dropout in Sjögren's syndrome and non-Sjögren's dry eye patients. 2018 Nov PURPOSE: The purpose of this study is to explore the differences in ocular symptoms and signs between Sjögren's syndrome (SS) and non-SS aqueous-deficient dry eye (ADDE) patients. METHODS: Twenty-two eyes of 22 SS patients (Group 1) and 22 eyes of 22 non-SS ADDE patients (Group 2) were enrolled. The evaluated variables included the Standard Patient Evaluation of Eye Dryness (SPEED), the Ocular Surface Disease Index (OSDI), tear meniscus height, first and average non-invasive keratographic breakup time (fNIKBUT and avNIKBUT), Schirmer I test, lipid layer thickness (LLT), meibomian gland expressibility, Marx line, corneal staining, conjunctival congestion, incomplete blinking, and meibomian gland dropout using two novel, non-invasive instruments, the Keratograph and LipiView II. RESULTS: Ocular signs of the NIKBUT (fNIKBUT: 3.8 (2.7, 5.2)s and 6.3 (3.7, 8.9)s, P = 0.024; avNIKBUT: 5.4 (4.5, 8.9)s and 7.6 (5.8, 13.7)s, P = 0.041), meibomian gland dropout of the upper eyelid (35.5% (29.1%, 54.8%) and 21.9% (16.7%, 24.9%), P = 0.000), and corneal staining (P = 0.050) were more severe but were associated with less severe symptoms, i.e., a lower SPEED score (P = 0.001), in SS subjects than in non-SS subjects. CONCLUSION: SS patients exhibit more severe meibomian gland destruction of the upper eyelid than non-SS patients. Meibomian gland dysfunction is another key cause of SS-associated dry eye.
30201146 Dermatoscopy of Granulomatous Disorders. 2018 Oct Although diagnosis of cutaneous granulomatous disorders (CGDs) is usually suspected based on morphologic findings, localization, and anamnestic data, clinical differentiation from each other and from similar dermatoses may be challenging. Recently, dermatoscopy has been demonstrated to be a useful tool for assisting the recognition of several CGDs. This article provides a current overview of the dermatoscopic features of the main noninfectious and infectious CGDs, including sarcoidosis, necrobiosis lipoidica, granuloma annulare, rheumatoid nodules, and leishmaniasis. Other, less common, CGDs are briefly addressed, including granulomatous rosacea, acne agminata, and leprosy.
29754136 Unravelling the NERDS syndrome. 2018 May 12 A 22-year-old man presented with symmetric polyarthritis, pruritus and deviation of angle of mouth to the right side since the last 7 years. His symptoms were persistent despite receiving ayurvedic medications and symptomatic therapy. Examination revealed dry skin, cutaneous nodules, xanthelasma, periarticular non-tender swellings, pitting oedema of hands and feet and lower motor neuron type right facial palsy. Haematological investigations revealed eosinophilia and skin biopsy had cutaneous eosinophilic infiltration. The constellation of above findings comprises the nodules, eosinophilia, rheumatism, dermatitis and swelling syndrome. It a rare syndrome with few reported cases in literature. The patient was started on oral corticosteroids which was subsequently tapered and methotrexate therapy. His polyarthritis and skin rashes resolved with therapy. He has been followed-up for 2 years and is presently asymptomatic for the last 1 year.
29743147 Incidence of sicca syndrome is 3.6 fold higher in areas with farm soils high in chromium a 2018 Aug BACKGROUND/PURPOSE: Chromium and nickel are important soil pollutants in Taiwan. Previously, we showed that blood chromium levels correlated strongly with soil chromium levels. Our observation that many patients with dry eyes or a dry mouth came from areas where soils contain high chromium levels prompted us to investigate whether incidence and prevalence of SS are higher in areas where soils contain high levels of heavy metals. METHODS: We used a database from national health insurance (NHI) to study the epidemiology of SS. It was ascertained by at least 3 hospital visits with the diagnosis within 12 months. We then compared the results with the information about heavy metal contents in farm soils. RESULTS: The incidence of SS was significantly increased (3.6 fold) in the areas where soils contained high levels of chromium and nickel. In contrast, lead, copper, or arsenic did not show such a strong association. CONCLUSION: Both the prevalence and incidence of SS are significantly increased in areas where soils contain high levels of chromium and nickel. Whether heavy metal, particularly chromium or nickel is a novel environmental risk factor for sicca syndrome needs more studies to confirm.
30075989 Risk of dementia among patients with Sjogren's syndrome: A nationwide population-based coh 2019 Apr OBJECTIVE: Autoimmunity may play a role in early-stage dementia. The association between Sjogren's syndrome (SS) and dementia remains unknown. This study was conducted to provide epidemiologic evidence for this relationship. METHODS: This 12-year, nationwide, population-based, retrospective cohort study analyzed the risk of dementia in the SS cohort. We also investigated the incidence of dementia among patients with SS by using data from the Longitudinal Health Insurance Database 2000, maintained by the Taiwan National Health Research Institutes. To balance the prevalence of characteristics in the cohorts, we used the propensity score to match selected comorbidities in the two cohorts. We also analyzed the association between SS and dementia among patients with different potential risks by using a Cox proportional hazard model. RESULTS: According to the analysis of data obtained from follow-up conducted during 2000-2012, the incidence of dementia in the SS cohort was 1.21-fold that in the control cohort (95% confidence interval [CI] = 1.02-1.45, p < 0.05). In the group older than 65years, the incidence of dementia was significantly high (adjusted hazard ratio [aHR] = 5.30, 95% CI = 4.26-6.60, p < 0.01). After adjustment for comorbidities, including Parkinson's disease (aHR = 2.98, 95% CI = 1.80-4.94), insomnia (aHR = 1.45, 95% CI = 1.14-1.85), and hypertension (aHR = 1.43, 95% CI = 1.19-1.71), the association between SS and dementia was still significant. CONCLUSION: This 13-year, nationwide, population-based retrospective cohort study revealed patients with SS to have a higher risk of dementia.
29850640 Parameters of Somatosensory Evoked Potentials in Patients with Primary SjÓ§gren's Syndrome 2018 Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease. The aim of the study was to establish whether in patients with pSS without central nervous system (CNS) involvement, the function of the central portion of the sensory pathway can be challenged. In 33 patients with pSS without clinical features of CNS damage and normal head computed tomography scan, somatosensory evoked potentials (SEP) were studied. The results were compared to other clinical parameters of the disease, particularly to immunological status. The control group consisted of 20 healthy volunteers. Mean latency of all components of SEP was considerably prolonged in patients compared to the control group. Mean interpeak latency N20-N13 (duration of central conduction TT) did not differ significantly between the groups. However, in the study group, mean amplitude of N20P22 and N13P16 was significantly higher compared to healthy individuals. In patients with pSS, significant differences in SEP parameters depending on the duration of the disease and presence of SSA and SSB antibodies were noted. The authors confirmed CNS involvement often observed in patients with pSS. They also showed dysfunction of the central sensory neuron as a difference in the amplitude of cortical response, which indicates subclinical damage to the CNS.
29251027 Efficacy and safety of tocilizumab with inhibition of interleukin-6 in adult-onset Still's 2018 Sep OBJECTIVES: Tocilizumab (TCZ) is the only available biologics inhibiting interleukin-6 presently, and emerging evidences have figured that elevated serum level of interleukin-6 is a crucial link of the pathogenesis of adult-onset Still's disease (AOSD). However, evidence about the efficacy and safety of TCZ in AOSD with strong power is still scarce. Thus, this meta-analysis was conducted to synthetically assess the efficacy and safety of TCZ on AOSD. METHODS: PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Chinese Biological Medical Literature database were comprehensively searched up to 31 July 2017 for the pertinent studies. The pooled remission rates were synthesized by fixed effect model or randomized effects model, depended on heterogeneity. RESULTS: Ten original studies contained 147 individuals were included in our analysis. The overall partial and complete remission rates were 85.38 (95% CI: 69.32-96.88%) and 77.91% (95% CI: 57.91-90.04%), respectively, and the remission rate of refractory patients was 87.92% (95% CI: 56.53-100.00%). CONCLUSION: The use of TCZ could significantly reduce the need of corticosteroids for AOSD patients. Impressive improvements were attained in both clinical and laboratory parameters. Compared with conventional therapy, TCZ treatment was safety. In conclusion, TCZ was effective and well tolerated for the treatment of AOSD.
29159471 Evidence for genetic overlap between adult onset Still's disease and hereditary periodic f 2018 Jan OBJECTIVE: Adult onset Still's disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD. METHODS: We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD. RESULTS: We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (p (c) = 2.34E- 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p (c) = 2.40E- 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. CONCLUSION: Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.
30603567 A Pathophysiological Validation of Collagenase II-Induced Biochemical Osteoarthritis Anima 2018 Aug BACKGROUND: Current dilemma working with surgically-induced OA (osteoarthritis) model include inconsistent pathological state due to various influence from surrounding tissues. On the contrary, biochemical induction of OA using collagenase II has several advantageous points in a sense that it does not involve surgery to induce model and the extent of induced cartilage degeneration is almost uniform. However, concerns still exists because biochemical OA model induce abrupt destruction of cartilage tissues through enzymatic digestion in a short period of time, and this might accompany systemic inflammatory response, which is rather a trait of RA (rheumatoid arthritis) than being a trait of OA. METHODS: To clear the concern about the systemic inflammatory response that might be caused by abrupt destruction of cartilage tissue, OA was induced to only one leg of an animal and the other leg was examined to confirm the presence of systemic degenerative effect. RESULTS: Although the cartilage tissues were rapidly degenerated during short period of time upon biochemical induction of OA, they did not accompanied with RA-like process based on the histology data showing degeneration of articular cartilage occurred only in the collagenase-injected knee joint. Scoring evaluation data indicated that the cartilage tissues in non-induced joint remained intact. Neutrophil count transiently increase between day 8 and day 16, and there were no significant change in other complete blood count profile showing a characteristics of OA disease. CONCLUSION: These study shows that biochemically induced cartilage degeneration truly represented uniform and reliable OA state.