Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.ArthritisArthritis, Experimental: ARTHRITIS that is induced in experimental animals. Immunological methods and infectious agents can be used to develop experimental arthritis models. These methods include injections of stimulators of the immune response, such as an adjuvant (ADJUVANTS, IMMUNOLOGIC) or COLLAGEN.Arthritis, Infectious: Arthritis caused by BACTERIA; RICKETTSIA; MYCOPLASMA; VIRUSES; FUNGI; or PARASITES.Arthritis, Juvenile: Arthritis of children, with onset before 16 years of age. The terms juvenile rheumatoid arthritis (JRA) and juvenile idiopathic arthritis (JIA) refer to classification systems for chronic arthritis in children. Only one subtype of juvenile arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.Arthritis, Psoriatic: A type of inflammatory arthritis associated with PSORIASIS, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of HLA-B27-associated SPONDYLARTHROPATHY, and the absence of rheumatoid factor.Arthritis, Reactive: An aseptic, inflammatory arthritis developing secondary to a primary extra-articular infection, most typically of the GASTROINTESTINAL TRACT or UROGENITAL SYSTEM. The initiating trigger pathogens are usually SHIGELLA; SALMONELLA; YERSINIA; CAMPYLOBACTER; or CHLAMYDIA TRACHOMATIS. Reactive arthritis is strongly associated with HLA-B27 ANTIGEN.Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.Joints: Also known as articulations, these are points of connection between the ends of certain separate bones, or where the borders of other bones are juxtaposed.Synovial Fluid: The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.Arthritis, Gouty: Arthritis, especially of the great toe, as a result of gout. Acute gouty arthritis often is precipitated by trauma, infection, surgery, etc. The initial attacks are usually monoarticular but later attacks are often polyarticular.Rheumatoid Factor: Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.Mice, Inbred DBASynovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. (Dorland, 27th ed)Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.Collagen Type II: A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Rats, Inbred LewAutoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Blood Sedimentation: Measurement of rate of settling of erythrocytes in anticoagulated blood.Injections, Intra-Articular: Methods of delivering drugs into a joint space.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Arthrography: Roentgenography of a joint, usually after injection of either positive or negative contrast medium.Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis.Knee Joint: A synovial hinge connection formed between the bones of the FEMUR; TIBIA; and PATELLA.Metacarpophalangeal Joint: The articulation between a metacarpal bone and a phalanx.Spondylitis, Ankylosing: A chronic inflammatory condition affecting the axial joints, such as the SACROILIAC JOINT and other intervertebral or costovertebral joints. It occurs predominantly in young males and is characterized by pain and stiffness of joints (ANKYLOSIS) with inflammation at tendon insertions.Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Gold Sodium Thiomalate: A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.Wrist Joint: The joint that is formed by the distal end of the RADIUS, the articular disc of the distal radioulnar joint, and the proximal row of CARPAL BONES; (SCAPHOID BONE; LUNATE BONE; triquetral bone).Rheumatoid Nodule: Subcutaneous nodules seen in 20-30% of rheumatoid arthritis patients. They may arise anywhere on the body, but are most frequently found over the bony prominences. The nodules are characterized histologically by dense areas of fibrinoid necrosis with basophilic streaks and granules, surrounded by a palisade of cells, mainly fibroblasts and histiocytes.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).HLA-DRB1 Chains: A subtype of HLA-DRB beta chains that includes over one hundred allele variants. The HLA-DRB1 subtype is associated with several of the HLA-DR SEROLOGICAL SUBTYPES.Finger Joint: The articulation between the head of one phalanx and the base of the one distal to it, in each finger.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Tarsal Joints: The articulations between the various TARSAL BONES. This does not include the ANKLE JOINT which consists of the articulations between the TIBIA; FIBULA; and TALUS.Lyme Disease: An infectious disease caused by a spirochete, BORRELIA BURGDORFERI, which is transmitted chiefly by Ixodes dammini (see IXODES) and pacificus ticks in the United States and Ixodes ricinis (see IXODES) in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. The disease was formerly known as Lyme arthritis and first discovered at Old Lyme, Connecticut.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.HLA-DR4 Antigen: An HLA-DR antigen which is associated with HLA-DRB1 CHAINS encoded by DRB1*04 alleles.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Joint DiseasesHLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.CitrullineCytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Spondylarthropathies: Heterogeneous group of arthritic diseases sharing clinical and radiologic features. They are associated with the HLA-B27 ANTIGEN and some with a triggering infection. Most involve the axial joints in the SPINE, particularly the SACROILIAC JOINT, but can also involve asymmetric peripheral joints. Subsets include ANKYLOSING SPONDYLITIS; REACTIVE ARTHRITIS; PSORIATIC ARTHRITIS; and others.Foot Joints: The articulations extending from the ANKLE distally to the TOES. These include the ANKLE JOINT; TARSAL JOINTS; METATARSOPHALANGEAL JOINT; and TOE JOINT.Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.Cartilage, Articular: A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.Ankle Joint: The joint that is formed by the inferior articular and malleolar articular surfaces of the TIBIA; the malleolar articular surface of the FIBULA; and the medial malleolar, lateral malleolar, and superior surfaces of the TALUS.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Interleukin-17: A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Freund's Adjuvant: An antigen solution emulsified in mineral oil. The complete form is made up of killed, dried mycobacteria, usually M. tuberculosis, suspended in the oil phase. It is effective in stimulating cell-mediated immunity (IMMUNITY, CELLULAR) and potentiates the production of certain IMMUNOGLOBULINS in some animals. The incomplete form does not contain mycobacteria.Tarsus, Animal: The region in the hindlimb of a quadruped, corresponding to the human ANKLE.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Tenosynovitis: Inflammation of the synovial lining of a tendon sheath. Causes include trauma, tendon stress, bacterial disease (gonorrhea, tuberculosis), rheumatic disease, and gout. Common sites are the hand, wrist, shoulder capsule, hip capsule, hamstring muscles, and Achilles tendon. The tendon sheaths become inflamed and painful, and accumulate fluid. Joint mobility is usually reduced.HLA-B27 Antigen: A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*27 allele family.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Organogold Compounds: Organic compounds that contain GOLD as an integral part of the molecule. Some are used as ANTIRHEUMATIC AGENTS. The term chrysotherapy derives from an ancient Greek term for gold.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Hand Joints: The articulations extending from the WRIST distally to the FINGERS. These include the WRIST JOINT; CARPAL JOINTS; METACARPOPHALANGEAL JOINT; and FINGER JOINT.Glucose-6-Phosphate Isomerase: An aldose-ketose isomerase that catalyzes the reversible interconversion of glucose 6-phosphate and fructose 6-phosphate. In prokaryotic and eukaryotic organisms it plays an essential role in glycolytic and gluconeogenic pathways. In mammalian systems the enzyme is found in the cytoplasm and as a secreted protein. This secreted form of glucose-6-phosphate isomerase has been referred to as autocrine motility factor or neuroleukin, and acts as a cytokine which binds to the AUTOCRINE MOTILITY FACTOR RECEPTOR. Deficiency of the enzyme in humans is an autosomal recessive trait, which results in CONGENITAL NONSPHEROCYTIC HEMOLYTIC ANEMIA.Disability Evaluation: Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for Social Security and workmen's compensation benefits.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Interleukin-6: A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.): Component of the NATIONAL INSTITUTES OF HEALTH. It supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress. It was established in 1986.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mice, Inbred C57BLCase-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.Borrelia burgdorferi: A specific species of bacteria, part of the BORRELIA BURGDORFERI GROUP, whose common name is Lyme disease spirochete.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Hindlimb: Either of two extremities of four-footed non-primate land animals. It usually consists of a FEMUR; TIBIA; and FIBULA; tarsals; METATARSALS; and TOES. (From Storer et al., General Zoology, 6th ed, p73)Yersinia Infections: Infections with bacteria of the genus YERSINIA.Arthralgia: Pain in the joint.Spondylarthritis: Inflammation of the joints of the SPINE, the intervertebral articulations.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Toe Joint: The articulation between the head of one phalanx and the base of the one distal to it, in each toe.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Glucocorticoids: A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.C-Reactive Protein: A plasma protein that circulates in increased amounts during inflammation and after tissue damage.Hand Deformities, Acquired: Deformities of the hand, or a part of the hand, acquired after birth as the result of injury or disease.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Bone Resorption: Bone loss due to osteoclastic activity.Matrix Metalloproteinase 3: An extracellular endopeptidase of vertebrate tissues similar to MATRIX METALLOPROTEINASE 1. It digests PROTEOGLYCAN; FIBRONECTIN; COLLAGEN types III, IV, V, and IX, and activates procollagenase. (Enzyme Nomenclature, 1992)Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Felty Syndrome: A rare complication of rheumatoid arthritis with autoimmune NEUTROPENIA; and SPLENOMEGALY.Foot: The distal extremity of the leg in vertebrates, consisting of the tarsus (ANKLE); METATARSUS; phalanges; and the soft tissues surrounding these bones.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Hand: The distal part of the arm beyond the wrist in humans and primates, that includes the palm, fingers, and thumb.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Sternoclavicular Joint: A double gliding joint formed by the CLAVICLE, superior and lateral parts of the manubrium sterni at the clavicular notch, and the cartilage of the first rib.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Metatarsophalangeal Joint: The articulation between a metatarsal bone (METATARSAL BONES) and a phalanx.Auranofin: An oral chrysotherapeutic agent for the treatment of rheumatoid arthritis. Its exact mechanism of action is unknown, but it is believed to act via immunological mechanisms and alteration of lysosomal enzyme activity. Its efficacy is slightly less than that of injected gold salts, but it is better tolerated, and side effects which occur are potentially less serious.Sjogren's Syndrome: Chronic inflammatory and autoimmune disease in which the salivary and lacrimal glands undergo progressive destruction by lymphocytes and plasma cells resulting in decreased production of saliva and tears. The primary form, often called sicca syndrome, involves both KERATOCONJUNCTIVITIS SICCA and XEROSTOMIA. The secondary form includes, in addition, the presence of a connective tissue disease, usually rheumatoid arthritis.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Protein Tyrosine Phosphatase, Non-Receptor Type 22: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an N-terminal catalytic domain and a C-terminal PROLINE-rich domain. The phosphatase subtype is predominantly expressed in LYMPHOCYTES and plays a key role in the inhibition of downstream T-LYMPHOCYTE activation. Polymorphisms in the gene that encodes this phosphatase subtype are associated with a variety of AUTOIMMUNE DISEASES.Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Spondylitis: Inflammation of the SPINE. This includes both arthritic and non-arthritic conditions.Osteitis: Inflammation of the bone.Mice, Inbred BALB CArthritis-Encephalitis Virus, Caprine: A species of LENTIVIRUS, subgenus ovine-caprine lentiviruses (LENTIVIRUSES, OVINE-CAPRINE), closely related to VISNA-MAEDI VIRUS and causing acute encephalomyelitis; chronic arthritis; PNEUMONIA; MASTITIS; and GLOMERULONEPHRITIS in goats. It is transmitted mainly in the colostrum and milk.Biological Therapy: Treatment of diseases with biological materials or biological response modifiers, such as the use of GENES; CELLS; TISSUES; organs; SERUM; VACCINES; and humoral agents.Biological Products: Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.Statistics, Nonparametric: A class of statistical methods applicable to a large set of probability distributions used to test for correlation, location, independence, etc. In most nonparametric statistical tests, the original scores or observations are replaced by another variable containing less information. An important class of nonparametric tests employs the ordinal properties of the data. Another class of tests uses information about whether an observation is above or below some fixed value such as the median, and a third class is based on the frequency of the occurrence of runs in the data. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1284; Corsini, Concise Encyclopedia of Psychology, 1987, p764-5)RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures.Epitopes: Sites on an antigen that interact with specific antibodies.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Early Diagnosis: Methods to determine in patients the nature of a disease or disorder at its early stage of progression. Generally, early diagnosis improves PROGNOSIS and TREATMENT OUTCOME.Questionnaires: Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Th17 Cells: Subset of helper-effector T-lymphocytes which synthesize and secrete IL-17, IL-17F, and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases.Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, or eating.Aurothioglucose: A thioglucose derivative used as an antirheumatic and experimentally to produce obesity in animals.Bone Diseases: Diseases of BONES.Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.Borrelia burgdorferi Group: Gram-negative helical bacteria, in the genus BORRELIA, that are the etiologic agents of LYME DISEASE. The group comprises many specific species including Borrelia afzelii, Borellia garinii, and BORRELIA BURGDORFERI proper. These spirochetes are generally transmitted by several species of ixodid ticks.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Proteoglycans: Glycoproteins which have a very high polysaccharide content.Spleen: An encapsulated lymphatic organ through which venous blood filters.Arthrodesis: The surgical fixation of a joint by a procedure designed to accomplish fusion of the joint surfaces by promoting the proliferation of bone cells. (Dorland, 28th ed)Range of Motion, Articular: The distance and direction to which a bone joint can be extended. Range of motion is a function of the condition of the joints, muscles, and connective tissues involved. Joint flexibility can be improved through appropriate MUSCLE STRETCHING EXERCISES.Arthroplasty, Replacement: Partial or total replacement of a joint.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system.Immunoconjugates: Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.Joint Prosthesis: Prostheses used to partially or totally replace a human or animal joint. (from UMDNS, 1999)Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Stifle: In horses, cattle, and other quadrupeds, the joint between the femur and the tibia, corresponding to the human knee.Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion.Osteoarthritis, Knee: Noninflammatory degenerative disease of the knee joint consisting of three large categories: conditions that block normal synchronous movement, conditions that produce abnormal pathways of motion, and conditions that cause stress concentration resulting in changes to articular cartilage. (Crenshaw, Campbell's Operative Orthopaedics, 8th ed, p2019)Tuberculosis, Osteoarticular: Tuberculosis of the bones or joints.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Foot Deformities, Acquired: Distortion or disfigurement of the foot, or a part of the foot, acquired through disease or injury after birth.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Elbow Joint: A hinge joint connecting the FOREARM to the ARM.Interleukin-10: A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Serum Albumin, Bovine: Serum albumin from cows, commonly used in in vitro biological studies. (From Stedman, 25th ed)Atlanto-Axial Joint: The joint involving the CERVICAL ATLAS and axis bones.Matrilin Proteins: PROTEOGLYCANS-associated proteins that are major components of EXTRACELLULAR MATRIX of various tissues including CARTILAGE; and INTERVERTEBRAL DISC structures. They bind COLLAGEN fibers and contain protein domains that enable oligomer formation and interaction with other extracellular matrix proteins such as CARTILAGE OLIGOMERIC MATRIX PROTEIN.Hip Joint: The joint that is formed by the articulation of the head of FEMUR and the ACETABULUM of the PELVIS.Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment; the overall condition of a human life.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Age of Onset: The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Arthroscopy: Endoscopic examination, therapy and surgery of the joint.Chondrocalcinosis: Presence of calcium salts, especially calcium pyrophosphate, in the cartilaginous structures of one or more joints. When accompanied by attacks of goutlike symptoms, it is called pseudogout. (Dorland, 27th ed)Matrix Metalloproteinases: A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Sacroiliac Joint: The immovable joint formed by the lateral surfaces of the SACRUM and ILIUM.Hand Bones: The CARPAL BONES; METACARPAL BONES; and FINGER PHALANGES. In each hand there are eight carpal bones, five metacarpal bones, and 14 phalanges.Terpenes: A class of compounds composed of repeating 5-carbon units of HEMITERPENES.Aggrecans: Large HYALURONAN-containing proteoglycans found in articular cartilage (CARTILAGE, ARTICULAR). They form into aggregates that provide tissues with the capacity to resist high compressive and tensile forces.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Bursa, Synovial: A fluid-filled sac lined with SYNOVIAL MEMBRANE that provides a cushion between bones, tendons and/or muscles around a joint.