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Background and Purpose. People with osteoarthritis (OA) of the knee who have pain generally exhibit decreased activity and physical deconditioning. This study investigated the effects of mechanical unweighting on knee pain and exercise responses in people with OA of the knee who have pain. Subjects. Four men and 23 women, with a mean age of 67.9 years (SD=11.3, range=50-88) and having a 12-year average duration of knee OA, participated. Methods. A mechanical unloading device enabled subjects to perform a modified Naughton treadmill exercise test at 0%, 20%, and 40% of body-weight support (BWS). Oxygen consumption ([VO.sub.2]), heart rate (HR), and perceived pain were measured during the last minute of each exercise stage. Results. Mechanical unweighting at 20% and 40% BWS decreased the [VO.sub.2] and HR responses to treadmill exercise but did not decrease knee pain during walking in this sample. Conclusion and Discussion. These findings indicate that treadmill exercise accompanied by BWS permits recommended training intensities to be obtained in elderly people with OA, but may not provide pain relief in this group. [Kline Mangione K, Axen K, Haas F. Mechanical unweighting effects on treadmill exercise and pain in elderly people with osteoarthritis of the knee. Phys Ther. 1996;76:387-394., Osteoarthritis (OA) of the knee is a common rheumatological disease characterized by pain, stiffness, and decreased range of motion.[1-4] Decreased activity due to knee pain can lead to physical deconditioning, [...]

An increase in bone mineral density (BMD) may protect women with osteoarthrosis (OA) of the spine against bone loss. BMD is a frequently used measurement for evaluating bone mass. Doctors evaluated 375 volunteer women aged 50-85 for evidence of OA and spinal abnormalities by X-raying their spines. They also tested these women for BMD in the spine, hip, and total body and measured bone turnover rates as indicated by levels of excreted pyridinoline and deoxpyridinoline, and serum bone specific alkaline phosphatase. A total of 340 of the 375 women had OA. All of the BMD measurements were higher in the women with OA as compared to those without OA. The women with OA tended to have fewer vertebral deformities as compared to the women without OA. There was a significant association between spinal OA, higher BMD and lower rates of bone turnover.

X-ray measurements of joint space width (JSW) in the knees of osteoarthritis (OA) patients appears to accurately measure cartilage thickness in the medial compartment but not the lateral compartment. The accuracy of JSW measurements in monitoring disease progression has been questioned. Twenty OA patients had JSW measurements followed by double contrast macroarthrograms of the same knee. During a contrast macroarthrogram, joint fluid is removed and a contrast dye injected that is taken up by the cartilage lining the joint. X-ray pictures are then taken at 5 X magnification for detailed evaluation. The sum of the cartilage widths of over the heads of the two bones making up the joint as measured by macroarthrogram was compared with the JSW measurement. JSW reliably measured cartilage width in the medial but not the lateral compartment of the knee. Therefore, JSW can be used to evaluate cartilage thinning and compression.

Cathepsin B appears to play a role in the pathological degeneration of joint cartilage in osteoarthritis (OA). Cathepsin B is an enzyme that can digest cartilage. Cylinders of the full thickness of cartilage down to the underlying bone were taken from the head of the thigh bone in patients having hip replacement surgery and from cadavers free of OA at postmortem. Sections were made parallel to the joint surface and assayed for cathepsin B content. Cathepsin B levels in OA patients in areas of normal cartilage and where cartilage was severely degraded were similar to control sample levels. In areas of active disease, cathepsin B levels were substantially higher. Its distribution correlated specifically with localized areas of tissue degeneration. At sites where cartilage regeneration was in progress, capthepsin B levels approached 20 times that of controls. Capthepsin B appears to play a role in the progress of disease and as an antagonist of healing.

Stromelysin 1, an enzyme that can degrade several of the various proteins forming cartilage matrix, appears to be involved in arthritic diseases. Other families of connective tissue enzymes also appear to be involved. Samples were taken from the joint linings of diseased joints from seven rheumatoid arthritis patients and three osteoarthritis patients. Cells were cultured and assayed and slides were analyzed for the presence and location of stromelysin 1 and 2, matrilysin, gelatinases A and B, and enzyme inhibiting factors TIMP-1 and 2. Stromelysin 1 was found throughout the joint in all cases, both bound to connective tissue and within cells, but stromelysin 2 was not present. Collagenase, gelatinase A, and matrilysin were found only in rheumatic joints, and their regional distribution suggested that their synthesis was restricted in location and episodic in nature. TIMP-1, but not TIMP-2, was seen in five samples. All of these patients had been treated with anti-inflammatory drugs.

Articular (joint) cartilage may be limited in its ability to repair itself. The ability of cartilage to develop into a predetermined form may regulate its growth and repair. Features common to osteoarthritic cartilage and to developing cartilage, such as cell proliferation, elevated matrix synthesis and morphogenesis, are discussed. The changes over time of tissue regulation in fetal cartilage, diseased cartilage, and aging cartilage are discussed. More information is needed on the relationship between tissue regulation and the body's ability to repair cartilage, especially in regard to aging and disease.

Examination of the synovial fluid of individuals with osteoarthritis by analytical electron microscopy and x-ray powder diffraction revealed that mineral crystals may exist in these fluids. Small amounts of calcium pyrophosphate dihydrate (CPPD) crystals and basic calcium phosphates (BCP) were found in samples of synovial fluid from 11 individuals with arthritis. Previously, it was thought that minerals did not exist in synovial fluid because conventional analysis techniques, such as light microscopy, could not detect them. There may be an association between the presence of CPPD and BCP and severity of osteoarthritis. Different concentrations of crystal may cause different effects in the course of the disease.

Bone mineral density (BMD) appears to be increased in some middle-aged women with early osteoarthritis (OA). Osteoarthritis is the most common form of arthritis and may involve degenerative changes in more than one joint. Lower BMD is associated with osteoporosis. A total of 979 women between the ages of 45 and 64 years had X-rays of their hands and knees. Lumbar spine and thigh bone BMD measurements were also taken for 579 of these women. Those with lumbar spine OA had lumbar spine bone density measurements 7.8% greater than women without lumbar spine OA. Women with generalized OA had BMD measurements 9.3% higher than women without OA. These results indicate that some women may be protected against osteoporosis by a bone mineral forming tendency but that this may increase their risk of OA.

The proteoglycans chondroitin-4-sulphate/dermatan sulphate (Ch4S/DS) and chondroitin-6-sulphate (Ch6S) may have distinct functions in normal and diseased synovium. Proteoglycans are found in connective tissue and act as binding material. Ch4S/DS and Ch6S are structurally identical but are found in different parts of synovial tissue. The synovium is a membrane which excretes a transparent fluid in joint cavities and tendons. Researchers examined synovial samples from four patients with osteoarthritis (OA), 10 patients with rheumatoid arthritis and six healthy subjects (control group). OA and RA are both joint diseases. Ch4S/DS was distributed throughout all synovial tissues and was found on blood vessels of RA samples. Ch6S was found in the lining layer of normal synovium but was absent from this site in both diseased samples. Ch6S was present on the blood vessels of all tissue samples.

An analysis of cytokines and synovial membranes (SMs) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) may not be helpful in diagnosing or distinguishing between the two conditions. Synovial membranes are found in the inner linings of joints. Cytokines are often found in the tissues of patients with joint diseases. Both RA and OA are degenerative diseases affecting the joints. Samples of synovial membranes from ten patients with RA and ten with OA were analyzed by immunohistochemistry. SMs from RA patients had thicker lining layers. This thickness may be specific to RA. Higher levels of cytokines were found in the SMs of RA patients than in OA patients. However, the similarity in cytokine expression between the two groups suggests that no single cytokine is particular to either disease. These findings indicate that cytokine production is a quantitative measure for RA and OA. More research is needed to determine patterns of joint destruction from patients with early stages of disease.

The presence of mature osteoclasts appears to be uncommon in the synovial fluid of patients with inflammatory or degenerative arthritis. Osteoclasts are cells associated with bone absorption and bone loss. It is not known whether immature osteocytes are recruited to a site and mature independently or whether immature cells in synovial fluid can differentiate into osteoclasts when synovial fluid comes into contact with bone. Synovial fluid samples were taken from 30 patients with rheumatoid arthritis and 29 patients with osteoarthritis. Levels of tartrate resistant acid phosphatase activity and vitronin receptor immunoreactivity were measured and used to indicate the presence of osteoclasts. Tartrate resistant acid phosphatase positive cells were found in synovial membranes from 60% of patients with RA and 69% of patients with OA. All 12 synovial membranes tested for vitronin receptor immunoreactivity were also positive. Despite the presence of osteoclast characteristics in synovial cells however, fully mature osteoclasts were uncommon in synovial fluid.

The presence of calcium crystals in the synovial fluid of the knees appears to be associated with the development of osteoarthritis. Three hundred osteoarthritic knees from 178 patients between the ages of 33 and 96 were examined. All patients had joint space loss in at least one compartment of the knee, but because many patients with osteoarthritis have symptoms only periodically or not at all, patients with and without knee symptoms were included. Calcium crystals were detected in 64% of the knees. The presence of calcium crystals was associated with a higher degree of joint space loss, hardening and bony growths. Calcium crystals were more likely to be detected in knees in which two or three compartments were osteoarthritic than in knees in which only one compartment was osteoarthritic. Patients with knees with two types of calcium crystals were more likely to have symptoms than than those with no crystals in their knees.

Tumor necrosis factor alpha (TNFa) is a protein which was originally identified in terms of its ability to cause tumor necrosis (death). However, it can affect other cells that regulate immune and inflammatory reactions. Studies suggest that TNFa may contribute to the tissue destruction that accompanies rheumatoid diseases. The protein has been found in joint fluid from patients with joint diseases, as has its RNA, genetic material coding for the protein, suggesting that TNFa is locally produced. However, the type of cell involved with TNFa production in joints is unknown. To better understand this, tissue specimens from 11 patients with rheumatoid arthritis (RA), four patients with osteoarthritis (OA), and four patients with other inflammatory joint diseases were assessed for TNFa content. Most RA and OA tissues but not normal synovial tissues stained for TNFa. In RA tissues, the synovial lining and deeper areas were positive for TNFa, as were some aggregates of lymphoid cells (type of white blood and tissue immune cells important for fighting infection) and cells lining blood vessels. In RA tissues, the protein was also present at the junction between cartilage and pannus (granulation tissue formed by inflamed synovium, which extends over cartilage and can burrow into bone). TNFa was chiefly found in OA tissues in layers below the synovial lining. Cells with surface proteins characteristic of macrophages, immune cells which are important in digesting particles and invading organisms, were the chief cells containing TNFa. The report supports a role for TNFa in the disease process underlying arthritis. (Consumer Summary produced by Reliance Medical Information, Inc.)

Many cells are implicated in the inflammatory process that occurs in arthritis. The role of mast cells (immune cells present in blood and tissue which mediate allergic and other reactions) present within synovium (tissue that lines joints) is not well understood. Molecules within the granules of mast cells can facilitate inflammation and thus can potentially intensify synovial inflammation. Synovial mast cell levels correlate with severity of disease in patients with rheumatoid arthritis (RA). To better understand the role of mast cells in arthritis, their presence was studied in tissues from 48 patients with RA and 42 patients with osteoarthritis (OA). There were significantly lower levels of mast cells in patients with active RA than in those with OA or inactive RA. Release of histamine (a hormone that mediates allergic and other reactions) by mast cells was greater from active RA patients. Among all patients, the 54 who were treated with nonsteroidal anti-inflammatory drugs (NSAIDs, such as aspirin or ibuprofen) had significantly fewer mast cells. Mast cells from RA patients who were being treated with low doses of steroids released significantly more histamine than those from RA patients not so treated. In contrast, histamine content was lower in mast cells from RA patients who were taking disease-modifying antirheumatic drugs (DMARDs) such as methotrexate or hydroxychloroquine. The study indicates that synovial mast cells are functionally different in RA and OA, and are affected by antirheumatic therapy. (Consumer Summary produced by Reliance Medical Information, Inc.)

Knowledge about the mechanisms of inflammation of synovial tissue, which forms the lining of joints, is necessary to understand the arthritic disease process. Technical problems in research on the proteins involved in this process have made this effort difficult. Technical advances now allow identification of proteins, or the genetic material such as messenger RNA (mRNA) that codes for them, without artifactual results. One relatively new method, in situ hybridization, has been used to study complement proteins (proteins usually found in blood that are important in fighting microorganisms), HLA-DR (a group of host defense proteins linked to tendency toward diseases such as arthritis), collagenase (an enzyme that degrades collagen and other structural proteins) and tissue inhibitor of metalloproteinases (TIMP, which blocks the action of collagenase) in synovial tissue from 12 patients with rheumatoid arthritis (RA), eight patients with osteoarthritis (OA), and three patients with other inflammatory joint diseases. The synovial lining layer was characterized by the presence of mRNA for collagenase, TIMP, and C2, one of the two complement proteins studied. HLA-DR was found in the lining as well, and in the sublining layer, particularly where aggregates of lymphocyte-like cells were present. The second complement protein, C3, was also present in lymphoid aggregates in the subsynovium. RA patients had higher levels of collagenase, C2, C3, and HLA-DR mRNA than did OA patients, while TIMP levels were similar. One sample of normal synovium, obtained at autopsy, had no collagenase, C2, or C3 present. Inflammation and erythrocyte sedimentation rate (an indicator of inflammatory or systemic disease) correlated strongly with levels of the proteins, and while TIMP was related to inflammation, levels were lower in RA than in OA samples. Levels of mRNA for all proteins correlated most strongly with the presence of lymphoid cells. Inflammation decreased in three patients due to local injection of steroids, and joint tissues had significantly lower levels of collagenase, HLA DR, TIMP (in three patients), and C3 or C2 mRNA (in one or two patients). The study provides insight into arthritic disease processes in arthritis, and will aid the design of new treatments. (Consumer Summary produced by Reliance Medical Information, Inc.)

Rheumatoid arthritis (RA) and osteoarthritis (OA) are characterized by degradation of molecules within connective tissue throughout affected joints. Among the proteinases (enzymes which break down proteins) that can do this, the metalloproteinases are thought to be particularly significant. Collagenase and stromelysin, along with the genetic material that codes for their production, have been found in the synovial layers (linings of joints) from RA patients. The activity of these enzymes is stimulated by several protein hormones, and inhibited by tissue inhibitor of metalloproteinases (TIMP), a protein found within joint tissues. To better understand how these proteins are regulated, the production of the two enzymes and inhibitor in joint tissues from six patients with RA, five with OA, and two with joint trauma was evaluated. The presence of messenger RNA (mRNA, a type of genetic material) coding for the proteins was detected with in situ hybridization, a genetic technique. Collagenase and stromelysin mRNA were both present in two types of cells in the synovial (joint lining) samples, macrophages (defensive cells which ingest invading organisms, often found in areas of inflammation) and fibroblasts (cells that give rise to connective tissue). TIMP was found in similar cells, and the amount produced appeared to be similar in patients with RA and OA. The enzymes and TIMP appeared to be produced together, but levels of the protein-degrading enzymes appeared to be greater than that of the inhibitor in active RA, while TIMP levels appeared to be greater than enzyme levels in OA samples. Proteinase levels were more strongly related to disease severity than to other physiological aspects of disease. It is concluded that the balance within the joint lining between destruction of collagen and inhibition of collagenase is upset in RA during inflammation, and that synovial tissue function differs in RA and OA. This information improves the ability to develop treatment strategies for RA. (Consumer Summary produced by Reliance Medical Information, Inc.)

Erosion of cartilage, bone, and other connective tissue occurs with the inflammatory process in rheumatoid arthritis (RA) and is thought to be mediated partly by two proteinases (enzymes that break down proteins), collagenase and stromelysin. Collagenase breaks down collagen, the body's main structural protein, while stromelysin is active against many molecules found in connective tissue. Recent studies in the laboratory and using tissue from humans suggest that the enzymes are produced in the synovial lining, a layer of tissue surrounding joints. To better understand the location and regulation of these two enzymes, the messenger RNA (mRNA, genetic material) carrying the codes for the structure of the two proteins was studied in tissue from eight patients with RA and two patients with osteoarthritis (OA). The mRNA for collagenase and for stromelysin was found in the same cells within the synovial lining layer in RA patients, indicating that production of the two proteins is coordinated. One OA patient had undetectable levels of metalloproteinase production, while the other had levels slightly below those in RA patients. Enzyme production tended to be focused rather than diffusely spread. Enzyme production tended to be related to hyperplasia (overgrowth) of the synovial lining layer. Information from this report and others using similar advanced techniques will increase understanding of the disease processes underlying OA and RA. (Consumer Summary produced by Reliance Medical Information, Inc.)

Hyaluronic acid (HA) is a large molecule made of many smaller sugar molecules. Its levels in blood are elevated in a number of diseases, including scleroderma, cirrhosis, and rheumatoid arthritis (RA). The increased levels may be due to decreased removal from blood (by the liver) or from increased production or release by tissue. HA levels correlate with physical activity in healthy subjects and with the amount of joint tissue in patients with RA. HA is synthesized by cells lining the joint surface, is present in high levels in synovial fluid (which lubricates joint surfaces), and helps maintain normal joint function. Increased blood levels of HA in RA may be due to disruption of joint tissues or to inflammatory processes. Osteoarthritis (OA), like RA, results in disruption of joint tissue, but the underlying disease processes differ. To better understand the implications of elevated blood levels of HA, levels were studied in 33 patients with OA, 33 patients with RA, and 10 healthy subjects. Compared with healthy subjects, HA levels were seven-fold higher in RA patients and two-fold higher in OA patients, but there was overlap in HA levels between the two patient groups. Levels of HA did not correlate with parameters related to inflammation or patient age in either the RA or OA group. In patients with OA, HA levels correlated with number of affected joints, including those with joint replacements. HA levels in OA patients also correlated with function. HA levels did not correlate with inflammatory parameters in six RA patients, who were evaluated over a six-month period. The results suggest that HA levels are not useful in discriminating between the presence of RA and OA. However, HA may be useful as an indicator of joint involvement in these arthritic diseases. (Consumer Summary produced by Reliance Medical Information, Inc.)

Interleukin-1 (IL-1) belongs to a family of proteins called cytokines. Cytokines are small proteins that are made by cells in the immune system (the body's natural defense system for fighting infection), by cells that form the inner lining of blood vessels (endothelial cells), and by cells in joint tissue (fibroblasts). IL-1 can produce a wide variety of effects in many different parts of the body. In the immune system, IL-1 plays an important role in activating certain T cells that kill microorganisms that invade the body, and it plays an important role in provoking an inflammatory response. In joint tissue, IL-1 causes enzymes to be made that can degrade or destroy the joint tissue. Osteoarthritis is a form of arthritis that destroys the joint tissue, and patients with this disease have high levels of these enzymes in their joints. Although the exact cause of osteoarthritis is unknown, IL-1 has been found in the joint fluid (synovial fluid) of patients with osteoarthritis, and it may be involved in the destruction of joint tissue. IL-1 has been found in the blood and in the joints of patients with rheumatoid arthritis. In a recent study, the amount of IL-1 present in the joints of patients with rheumatoid arthritis appeared to be related to the severity of the disease. It is not known if IL-1 causes arthritis or if IL-1 is made during the course of the disease. The exact role that IL-1 plays in arthritis remains to be determined. (Consumer Summary produced by Reliance Medical Information, Inc.)

Osteoarthritis (OA) is a degenerative disease. In the hip, OA can develop from mechanical stresses related to weight-bearing and motion and from biochemical unhealed alterations of cartilage. While cartilage disruption may not cause symptoms, progressive changes in the underlying bone, synovial tissue lining the joint, and nearby structures are usually associated with the symptoms of OA. Osteoarthritis is sometimes difficult to distinguish from other joint diseases, and the American College of Rheumatology (ACR) has been examining the symptoms, laboratory and X-ray signs that are most strongly associated with OA in different joint groups. Two sets of criteria for diagnosing OA of the hip are based on clinical and laboratory findings, and a combination of clinical, laboratory, and X-ray findings. These criteria were developed by studying 114 patients with OA and 87 patients with other hip disorders. Clinical findings associated with hip OA included pain plus one of two groups of findings: reduced motion (internal rotation) of the hip and an erythrocyte sedimentation rate of less than or equal to 45 millimeters per hour (mm/hr), or painful internal rotation, duration of hip stiffness under one hour, and patient age under 50 years. (Erythrocyte sedimentation rate, ESR, is a blood test that is a nonspecific indicator of diseases, especially inflammatory conditions.) When clinical, laboratory and X-ray findings were combined, the best criteria for diagnosing OA were hip pain plus at least two of three findings: ESR of less than 20 mm/hr, X-ray evidence of osteophytes (bony outgrowths) and/or narrowing of the joint space. This second group of criteria was more sensitive to OA diagnosis and excluded more cases involving other hip disorders. The criteria described are expected to promote more uniform diagnosis and reporting of OA. (Consumer Summary produced by Reliance Medical Information, Inc.)

Certain joint diseases, such as rheumatoid arthritis and osteoarthritis, are associated with the breakdown of proteoglycans (PG), which are found in the cartilage tissue of the joint. Keratan sulfate (KS) is a PG breakdown product and epitope, or portion of the PG molecule that attaches specific antibody, or immune protein. The measurement of KS levels may serve as a method of monitoring the progression of joint disease. The blood levels of KS epitope were measured in patients with joint diseases, including rheumatoid arthritis, osteoarthritis, and fibromyalgia, and in subjects without joint disease. Fibromyalgia is characterized by pain, tenderness, and stiffness of joints and related structures without joint cartilage destruction. The results showed that the KS levels were higher in patients with rheumatoid arthritis and osteoarthritis than in patients with fibromyalgia or in normal subjects. KS levels in patients with rheumatoid arthritis and osteoarthritis were not correlated with disease duration or joint score, a standard measure of joint function. The KS fragments were analyzed and found to be associated with protein core fragments of the proteoglycans. These findings show that although KS levels increase with cartilage deterioration, they do not indicate the extent or duration of joint disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Osteoarthritis is a chronic joint disease characterized by destruction of joint cartilage and overgrowth, malformation, and impaired function of the joint. The relation between degeneration of the cartilage tissue in the joint, determined by direct visual (arthroscopic) examination of the joint, and narrowing of the joint space, as indicated by X-ray, was assessed. The study involved 161 patients with chronic knee pain, and most subjects had X-ray evidence of mild osteoarthritis. Seventy-six patients had X-ray evidence of joint space narrowing (JSN) at the tibiofemoral joint at the knee, and 25 of these patients had normal joint cartilage tissue. Sixty-one patients with normal cartilage tissue at the medial joint also had no evidence of JSN. Twenty-two patients had medial JSN of greater than 50 percent, including nine with normal cartilage tissue at the medial joint. Thirty-six patients with greater than 25 percent narrowing had no evidence of cartilage tissue degeneration at the medial and lateral compartments of the joint. However, of these 36 patients, degeneration was detected in the cartilage tissue of the patellofemoral compartment, or front portion, of the knee joint in eight patients; in the meniscus (a crescent-shaped, fiber-like, cartilage structure of the knee joint) in 18 patients; and in both the meniscus and cartilage tissue of the patellofemoral compartment in eight patients. These findings show that X-ray evidence of JSN in the tibiofemoral compartment of the knee joint is not consistently associated with cartilage tissue degeneration in the joint. (Consumer Summary produced by Reliance Medical Information, Inc.)

Osteoarthritis, the most frequent type of arthritis, is related to age and most frequently affects the hip and knee (two important weight-bearing joints) and hand. However, concepts of causes and assessment of osteoarthritis are not well developed. Several factors appear to contribute to occurrence of the disease, including age, inheritance, body weight, and alterations in joint structure and function. To better characterize osteoarthritis, its occurrence in multiple joints of 500 people (342 female) referred to rheumatic specialists were evaluated. Although the group studied was probably not entirely representative of the total population affected by osteoarthritis, since those in the group received special medical referrals, the large number studied still might allow development of valid conclusions. Of 847 abnormal joints, 41 percent were knees, 30 percent were hands, and 19 percent were hips. Roughly half of patients had only one affected joint, and this single-site disease was more common among men and tended to decrease with age, a significant finding. Thirty-six percent of patients had two-site disease, chiefly women affected in the knees and hands. In general, women had shoulder and hand involvement, while men were most frequently affected in the hip and elbow. Obvious causes such as trauma were found in 18 percent of men and 5 percent of women, a lower incidence than suggested by other reports. Hypertension was found in 37 percent of patients, while 50 percent of women and 60 percent of men were overweight. The patients used medications frequently and often depended on functional appliances such as canes. Fewer cases of hip disease were found than expected, possibly because those had been referred for surgery. A significant number of patients had another rheumatic disease, but this was likely an artifact of the referral process. Hip and knee involvement was often associated with obesity or other predisposing cause. Heberden's nodes, enlargement of the outermost finger joints, was associated with multiple-joint disease, excess body weight, and hypertension, suggesting a background predisposition to the disease. The other trends observed indicate that the distribution and occurrence of osteoarthritis is not entirely random. More extensive study of these features are needed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cytokines are naturally occurring factors that function in inflammation and tissue repair, but are also capable of causing tissue damage and contributing to the disease process in rheumatoid arthritis (RA), an inflammatory joint disease. Interleukin-1-beta (IL-1-beta), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interferon alpha, and interferon-gamma are all cytokines. IL-1-beta and TNF-alpha can cause deterioration of the bone and cartilage tissue, and can activate the production of factors that contribute to the destructive process in RA, such as prostaglandins, proteases, and highly reactive oxygen species. Cytokines may also activate the expression of genes, such as the major histocompatibility gene complex, which controls the production of inflammatory cells and factors. The relationship of cytokine activity in synovial (joint) fluid to diagnosis or disease pattern was assessed in 68 patients with either inflammatory or non-inflammatory joint disease. The levels of IL-1-beta, IL-2, TNF-alpha, and the interferons alfa and gamma were measured in patients with RA, osteoarthritis, and spondarthritis, an inflammatory disease of the vertebrae. IL-1-beta levels in synovial fluid were highest in patients with RA, intermediate in patients with spondarthritis, and lowest in patients with osteoarthritis. IL-2 and TNF-alpha were lower in RA and spondarthritis than in osteoarthritis, a non-inflammatory joint disease. IL-2 levels were correlated with TNF-alpha levels in all patients, but there was no relationship between IL-1-beta levels and IL-2 or TNF-alpha levels, or between the interferons and the other cytokines. A variety of cytokine patterns were identified. Two control subjects without arthritis had lower levels of IL-1-beta but higher levels of other cytokines as compared with arthritic patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cytokines, factors released by cells, are involved in various cellular functions, such as production of proteins and chemicals, cell growth, and the chemical attraction of other cells. They are thought to be involved in the disease process of rheumatoid arthritis (RA), and are present in both the synovial fluid and synovial tissues in joints. Recent studies have suggested that the types of cytokines in the joints are limited. Previous studies of the types and quantities of cytokines present in the joints have been with immunological or biological tests, which have a number a technical difficulties associated with them. This study uses the molecular biological technique known as in situ hybridization to quantitate the expression of genes that encodes cytokines in cells of synovial fluid, synovial tissues, and intact synovial tissue from patients with RA. In situ hybridization uses a nucleotide probe specific for particular cytokines; it binds to messenger RNA in the cells and is synthesized into the cytokines. A large number of cells in the synovial tissues expressed the cytokines, indicating intense activation. The cytokines interleukin (IL)-6, IL-1beta, tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, and transforming growth factor-beta1 were present, and the levels of each cytokine were determined. By examining intact synovium, it was shown that the macrophage-like and fibroblast-like cells produced the cytokines, not synovial fluid cells or T lymphocytes found in the synovium. When synovial tissues from patients with osteoarthritis were analyzed, the same cytokines were found and in similar amounts. There was one exception; IL-6 was present in smaller quantities in osteoarthritis. It does not appear that a particular cytokine is responsible for the disease state in rheumatoid arthritis. The findings also indicate that the cytokines are similar in RA and osteoarthritis. (Consumer Summary produced by Reliance Medical Information, Inc.)

It is possible that swelling in the bone marrow causes the pain that most patients with osteoarthritis feel. Many patients have pain even though their joint disease is not severe and many patients with severe disease don't have pain. But the bone marrow may be injured and this may be what causes the pain.

Matrix metalloproteinase (MMP) activity appears to be greater in the synovial fluid of joints in young horses and horses with osteoarthritis (OA), compared to adult horses. MMPs are enzymes associated with cartilage growth and remodeling in joints. Researchers compared MMP levels in joint fluid samples from juvenile and adult horses and horses with OA or osteochondrosis. In healthy horses, MMP activity declined with age, indicating declining cartilage growth with age. In horses with OA, MMP activity was elevated, consistent with the cartilage destruction in this inflammatory condition. Osteochondrosis was not associated with increased MMP activity.