chronic inflamation and osteoarthritis. full text

[문형철]

만성염증은 지금 나에게 남은 몇가지 해결되지 않은 만성통증과 관절파괴의 원인이다.

그 문제 이해를 위한 term이 plasma cell ...

조직학책에 의하면

"형질세포plasma cell은 체내 대부분의 결합조직에서 그 수가 매우 적다. 이들은 박테리아나 이종단백질이 침투하기 쉬운곳과 만성염증이 있는 곳에 많이 존재한다"

바로 구글, pubmed검색에 들어가 논문 검색.

참고) 1: Lancet. 2005 Mar 12-18;365(9463):965-73. Links

Pathogenesis and management of pain in osteoarthritis.

Dieppe PA, Lohmander LS.

MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK. p.Dieppe@bristol.ac.uk

The term osteoarthritis describes a common, age-related, heterogeneous group of disorders characterised pathologically by focal areas of loss of articular cartilage in synovial joints, associated with varying degrees of osteophyte formation, subchondral bone change, and synovitis. Joint damage is caused by a mixture of systemic factors that predispose to the disease, and local mechanical factors that dictate its distribution and severity. Various genetic abnormalities have been described, but most sporadic osteoarthritis probably depends on minor contributions from several genetic loci. Osteoarthritic joint damage may be associated with clinical problems, but the severity of joint disease is only weakly related to that of the clinical problem. For this reason the associations and pathogenesis of pain are in as much need of investigation as joint damage. Subchondral bone and synovium may be responsible for nociceptive stimuli, and peripheral neuronal sensitisation is an important feature, and can result in normal activities (such as walking) causing pain. Central pain sensitisation can also occur, and psychosocial factors are important determinants of pain severity. We present a stepwise

Chronic inflammation is more difficult to understand, bcause it is so variable. Seen here is chronic endometritis with lymphocytes as well as plasma cells in the endometrial stroma. In general, the inflammatory infiltrate of chronic inflammation consists mainly of mononuclear cells ("round cells"): lymphocytes, plasma cells, and macrophages.

1: Osteoarthritis Cartilage. 2008 Sep 18. [Epub ahead of print] Links

Eval‎uation of a Photographic Ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy Score (PCS) for pathological samples in a study of inflammation in tibiofemoral osteoarthritis.

Walsh DA, Yousef A, McWilliams DF, Hill R, Hargin E, Wilson D.

Academic Rheumatology, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK; Back Pain Unit, Sherwood Forest Hospitals NHS Foundation Trust, Mansfield Road, Sutton in Ashfield NG17 4JL, UK.

OBJECTIVE: Severity of structural change in knee osteoarthritis (OA) can be measured radiologically, macroscopically or microscopically. Existing methods have limitations for use in laboratory studies. We have developed a Photographic Ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy Score (PCS) for use with pathological samples. We have compared the ability of the different severity measures to distinguish between samples obtained at total knee replacement surgery or postmortem (PM), and to detect associations between structural severity and synovitis. METHOD: Tibial plateaux and femoral condyles were collected from 84 patients undergoing surgery or PM. Each sample was photographed and scored. Limits of agreement and repeatability coefficients were calculated for PCS. Scores for radiological joint space narrowing (JSN) and osteophytes, histological cartilage changes (Mankin), and synovitis were assigned. Data were analysed using Mann-Whitney U tests, Spearman's correlation coefficient or logistic regression. RESULTS: A total of 116 knees were analysed from 84 patients. Both medial tibial plateaux and total joint PCS showed good repeatability, internal consistency and reliability between observers. PCS, radiographic and Mankin's scores were all modestly positively correlated (r values 0.28-0.55). PCS and Mankin scores were greater in surgical than PM samples. Synovial inflammation was associated with higher PCS and radiological JSN scores (r values 0.43-0.48), irrespective of diagnosis. CONCLUSION: Macroscopic, microscopic and radiographical severity scores are complementary measures of structural severity in knee OA. Synovial inflammation was associated with increased OA structural severity, suggesting a possible role of chronic synovitis in cartilage damage.

1: Osteoarthritis Cartilage. 2005 May;13(5):361-7. Links

Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis -- results of a 1 year longitudinal arthroscopic study in 422 patients.

Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M.

Service de Rhumatologie B, Hôpital Cochin, AP-HP, Université René Descartes, Paris, France. xavier.ayral@cch.ap-hop-paris.fr

OBJECTIVE: To eval‎uate the preval‎ence of synovitis in painful medial tibiofemoral knee osteoarthritis (OA) and to eval‎uate correlation between synovitis and the structural severity and progression of tibiofemoral cartilage damage. DESIGN: STUDY: Multicenter, longitudinal, 1-year duration. PATIENTS: Primary painful knee OA (ACR criteria) of the medial tibiofemoral compartment, with pain of the signal knee on at least 30 days in the past 2 months, medial joint space width > or = 2mm, at least 10% of one cartilage surface of the medial compartment affected by superficial fibrillation or worse at baseline arthroscopy. ARTHROSCOPIC PARAMETERS: Knee arthroscopy under local anesthesia was performed and videorecorded at entry and after 1 year. Medial ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy was scored by using Societe Francaise d'Arthroscopie (SFA) score (0-100) and reader's overall assessment (VAS score, 100 mm). Progression of medial ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy was defined by a change in SFA and VAS scores over 4.5 and 8.0 mm after 1 year, respectively. Medial perimeniscal synovium was scored as normal (few translucent and slender villi, fine vascular network), reactive (proliferation of opaque villi), or inflammatory (hypervascularization and/or proliferation of hypertrophic and hyperemic villi). Medial ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy and synovitis were scored by a single reader blind to chronology of paired videotapes. RESULTS: Four hundred and twenty-two patients were enrolled (mean age: 61 years, females: 59%, body mass index: 31, mean disease duration: 4 years) and completed the 1-year study. Synovial abnormalities were present in 50% of the patients with reactive and inflammatory aspects in 29% and 21% of the patients, respectively. Patients with a reactive or inflammatory medial synovium had a more severe medial ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy. The worsening in medial ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy after 1 year was statistically more severe in the group of patients with an inflammatory perimeniscal synovial membrane at baseline compared to patients with normal and reactive aspects, with no difference between these two latter groups. The odds ratio for progression in VAS score after 1 year was 3.11 (95% CI [1.07, 5.69]) for patients with inflammatory synovium at baseline compared to patients with normal synovium. CONCLUSIONS: This study suggests that abnormalities of the medial perimeniscal synovium are a common feature of painful medial knee OA, associated with more severe medial ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy. It also suggests that an inflammatory aspect of the medial perimeniscal synovium could be considered as a predictive factor of subsequent increased degradation of medial ch[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-[안내]태그제한으로등록되지않습니다-ondropathy.

1: Osteoarthritis Cartilage. 2008 Aug;16(8):873-82. Epub 2008 Feb 15. Links

Joint space narrowing and Kellgren-Lawrence progression in knee osteoarthritis: an analytic literature synthesis.

Emrani PS, Katz JN, Kessler CL, Reichmann WM, Wright EA, McAlindon TE, Losina E.

Orthopaedic and Arthritis Center for Outcomes Research, Department of Orthopaedic Surgery, Brigham and Women's Hospital, Boston, MA 02115, United States.

OBJECTIVE: While the interpretation of cartilage findings on magnetic resonance imaging (MRI) evolves, plain radiography remains the standard method for assessing progression of knee osteoarthritis (OA). We sought to describe factors that explain variability in published estimates of radiographic progression in knee OA. DESIGN: We searched PubMed between January 1985 and October 2006 to identify studies that assessed radiographic progression using either joint space narrowing (JSN) or the Kellgren-Lawrence (K-L) scale. We extracted cohort characteristics [age, gender, and body mass index (BMI)] and technical and other study factors (radiographic approach, study design, OA-related cohort composition). We performed meta-regression analyses of the effects of these variables on both JSN and K-L progression. RESULTS: Of 239 manuscripts identified, 34 met inclusion criteria. The mean estimated annual JSN rate was 0.13 +/- 0.15 mm/year. While we found no significant association between JSN and radiographic approach among observational studies, full extension was associated with greater estimated JSN among randomized control trials (RCTs). Overall, observational studies that used the semi-flexed approach reported greater JSN than RCTs that used the same approach. The overall mean risk of K-L progression by at least one grade was 5.6 +/- 4.9%, with higher risk associated with shorter study duration, OA definition (K-L > or = 2 vs K-L > or = 1) and cohorts composed of subjects with both incident and preval‎ent OA. CONCLUSION: While radiographic approach and study design were associated with JSN, OA definition, cohort composition and study duration were associated with risk of K-L progression. These findings may inform the design of disease modifying osteoarthritis drug (DMOAD) trials and assist clinicians in optimal timing of OA

1: J Cell Physiol. 2007 Dec;213(3):626-34. Links

Osteoarthritis.

Goldring MB, Goldring SR.

Laboratory for Cartilage Biology, Research Division, The Hospital for Special Surgery, Weill College of Medicine of Cornell University, New York 10021, USA. goldringm@hss.edu

Osteoarthritis (OA) is characterized by degeneration of articular cartilage, limited intraarticular inflammation with synovitis, and changes in peri-articular and subchondral bone. Multiple factors are involved in the pathogenesis of OA, including mechanical influences, the effects of aging on cartilage matrix composition and structure, and genetic factors. Since the initial stages of OA involve increased cell proliferation and synthesis of matrix proteins, proteinases, growth factors, cytokines, and other inflammatory mediators by chondrocytes, research has focused on the chondrocyte as the cellular mediator of OA pathogenesis. The other cells and tissues of the joint, including the synovium and subchondral bone, also contribute to pathogenesis. The adult articular chondrocyte, which normally maintains the cartilage with a low turnover of matrix constituents, has limited capacity to regenerate the original cartilage matrix architecture. It may attempt to recapitulate phenotypes of early stages of cartilage development, but the precise zonal variations of the original cartilage cannot be replicated. Current pharmacological interventions that address chronic pain are insufficient, and no proven structure-modifying therapy is available. Cartilage tissue engineering with or without gene therapy is the subject of intense investigation. There are multiple animal models of OA, but there is no single model that faithfully replicates the human disease. This review will focus on questions currently under study that may lead to better understanding of mechanisms of OA pathogenesis and elucidation of effective strategies for therapy, with emphasis on mechanisms that affect the function of chondrocytes and interactions with surrounding tissues. 2007 Wiley-Liss, Inc.

1: Best Pract Res Clin Rheumatol. 2006 Oct;20(5):1003-25. Links

Update on the biology of the chondrocyte and new approaches to treating cartilage diseases.

Goldring MB.

Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, New England Baptist Bone and Joint Institute and Harvard Medical School, Boston, MA 02115, USA. mgoldrin@bidmc.harvard.edu

Osteoarthritis (OA) is a joint disease that involves degeneration of articular cartilage, limited intraarticular inflammation manifested by synovitis and changes in the subchondral bone. The aetiology of OA is largely unknown, but since it may involve multiple factors, including mechanical, biochemical and genetic factors, it has been difficult to identify unique targets for therapy. Chondrocytes, which are the unique cellular component of adult articular cartilage, are capable of responding to structural changes in the surrounding cartilage matrix. Since the initial stages of OA involve increased cell proliferation and synthesis of matrix proteins, proteinases and cytokines in the cartilage, laboratory investigations have focused on the chondrocyte as a target for therapeutic intervention. The capacity of the adult articular chondrocyte to regenerate the normal cartilage matrix architecture is limited, however, and the damage becomes irreversible unless the destructive process is interrupted. Current pharmacological interventions that address chronic pain are insufficient and no proven disease-modifying therapy is available. Identification of methods for early diagnosis is of key importance, since therapeutic interventions aimed at blocking or reversing structural damage will be more effective when there is the possibility of preserving normal homeostasis. At later stages, cartilage tissue engineering with or without gene therapy with anabolic factors will also require therapy to inhibit inflammation and block damage to newly repaired cartilage. This review will focus on experimental approaches currently under study that may lead to elucidation of effective strategies for therapy in OA, with emphasis on mediators that affect the function of chondrocytes and interactions with surrounding tissues.

1: Rheumatology (Oxford). 2005 Jan;44(1):7-16. Epub 2004 Aug 3. Links

Osteoarthritis, angiogenesis and inflammation.

Bonnet CS, Walsh DA.

Academic Rheumatology, University of Nottingham, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK.

Angiogenesis and inflammation are closely integrated processes in osteoarthritis (OA) and may affect disease progression and pain. Inflammation can stimulate angiogenesis, and angiogenesis can facilitate inflammation. Angiogenesis can also promote chondrocyte hypertrophy and endochondral ossification, contributing to radiographic changes in the joint. Inflammation sensitizes nerves, leading to increased pain. Innervation can also accompany vascularization of the articular cartilage, where compressive forces and hypoxia may stimulate these new nerves, causing pain even after inflammation has subsided. Inhibition of inflammation and angiogenesis may provide effective therapeutics for the treatment of OA by improving symptoms and retarding joint damage. This review aims to summarize (i) the evidence that angiogenesis and inflammation play an important role in the pathophysiology of OA and (ii) possible directions for future research into therapeutics that could effectively treat this disease.

1: J Rheumatol. 1997 Feb;24(2):365-71. Links

Synovial membrane inflammation and cytokine production in patients with early osteoarthritis.

Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M.

Department of Rheumatology, Repatriation General Hospital, Daw Park, Australia.

OBJECTIVE: To establish the presence of inflammation in and cytokine production by synovial membranes from patients with various stages of early osteoarthritis (OA), with knee pain, normal knee radiographs, and arthroscopic evidence of chondral damage. METHODS: Synovial membrane samples were obtained from the knees of 63 patients at the time of arthroscopy for unexplained knee pain or at the time of joint replacement surgery. Eval‎uations of synovial membrane variables including thickness of lining layer, vascularity, and inflammatory cell infiltrate were by a blinded observer. In a subset of 20 patients, production of interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and protein levels was determined using in situ hybridization with biotin labeled ribo-probes and immunohistochemistry. RESULTS: There was evidence of thickening of the lining layer, increased vascularity, and inflammatory cell infiltration in synovial membranes from patients with all grades of OA, with the most marked changes seen in synovial tissue from patients with advanced grades of OA. Similarly, production of IL-1 alpha, IL-1 beta, and TNF-alpha was present in synovial membranes from all patients with OA, irrespective of the degree of articular cartilage damage. There was a trend to decreased levels of IL-1ra in synovial membranes from patients with OA that did not attain statistical significance. Similarly, there was a decrease in the ratio of IL-1ra to IL-1 alpha and beta with increasing grades of OA. CONCLUSION: Chronic inflammatory changes with production of proinflammatory cytokines are a feature of synovial membranes from patients with early OA, with the most severe changes seen in patients at the time of joint replacement surgery resembling those seen in rheumatoid arthritis. This low grade synovitis results in the production of cytokines that may contribute to the pathogenesis of OA.

1: J Rheumatol. 1990 Dec;17(12):1662-9. Links

Synovial inflammation in patients with early osteoarthritis of the knee.

Myers SL, Brandt KD, Ehlich JW, Braunstein EM, Shelbourne KD, Heck DA, Kalasinski LA.

Rheumatology Division, Indiana University School of Medicine, Indianapolis 46202-5103.

While synovitis is common in advanced osteoarthritis (OA), its preval‎ence and severity in patients with early or mild OA are uncertain. In our study synovial biopsies from patients with arthroscopic evidence of OA whose radiographs were normal, or showed only mild/moderate changes of OA, were examined to determine the preval‎ence and severity of lining cell proliferation and mononuclear cell infiltration. Synovitis was present in only 16 of 29 patients (55%) who underwent arthroscopy because of chronic knee pain and were found to have OA; no synovium from 50% of the 22 patients in this group with full thickness cartilage ulceration showed infiltration with mononuclear cells. Similarly, no evidence of synovitis was seen in biopsies from 7 of 14 additional patients with OA who did not have knee pain but who underwent arthroscopy to eval‎uate joint instability. An association was seen between synovial mononuclear cell infiltration and thickness of the synovial lining cell layer (p less than 0.03), but lining cell hyperplasia was found in samples from only 12% of the patients with OA in our series. The severity of OA cartilage lesions was unrelated to severity of synovitis and no topographic relationship was found between cartilage ulceration and synovitis.

1: Semin Arthritis Rheum. 1995 Oct;25(2):75-86. Links

Acute-phase proteins in osteoarthritis.

Sipe JD.

Department of Biochemistry, Boston University School of Medicine, MA 02118, USA.

The joint destruction of osteoarthritis (OA) comprises loss of articular cartilage resulting from an imbalance of enzyme-catalized cartilage breakdown and regeneration. OA is thought to derive from defective chondrocyte metabolism and thus to inherently lack the large-scale systemic response that is the hallmark of rheumatoid arthritis (RA). Because of the apparent absence of systemic inflammation in OA, acute-phase response proteins have not been as extensively studied in OA as they have been in RA. The diagnosis of OA almost always involves radiographic assessment of joint damage, which is useful only after the disease process has been underway for several months. Radiographic eval‎uation cannot give a good assessment of current disease activity and is a relatively insensitive indicator of prognosis. Cartilage breakdown products can potentially serve as direct surrogate markers of OA disease activity, but have not been extensively used because of their limited sensitivity and the technical difficulties associated with their measurement. Markers of disease activity in RA are indirect and are derived from the acute-phase response, a cycle of temporal changes in cellular and metabolic function. The early part of the acute-phase response involves the local action and production of cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF-alpha) and IL-6. In the late acute-phase response, these cytokines can effect many systemic changes, including increased production of acute-phase proteins (APP). Three valuable surrogate markers of disease activity in RA are provided by the acute-phase response: the time-honored erythrocyte sedimentation rate (ESR) and the newer APPs C-reactive protein (CRP) and serum amyloid A (SAA). As in RA, the joint destruction of OA involves IL-1, TNF-alpha, and IL-6; however, OA can be viewed as an indolent stimulus of the later (systemic) acute-phase response. Recent studies of the acute-phase response in OA suggest that the concentrations of CRP and SAA are elevated in OA, but to a lesser extent than in RA. In the future, long-term monitoring of CRP concentrations in the blood may permit the earlier detection and more effective treatment of OA.

chronic inflamation and plasma cell.pdf

panic bird.....