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Objective: To determine serum and synovial fluid (SF) concentrations of monocyte chemoattractant protein-1 (MCP-1) or CCL2 chemokine, in patients suffering (RA) and osteoarthritis (OA) and to correlate the values to disease activity, and other patient- and disease-related parameters., Methods: The CCL-2/MCP-1 chemokine (CK) was measured in serum and SF of 30 RA and 15 OA patients using specific and very sensitive ELISA assay., Results: The CCL2/MCP-1 CK was found in increased amounts in SF compared to serum (p < 0.001) and in RA compared to OA patients (p < 0.001). The values were significantly greater in RA patients with more active disease. Greater mean SF concentrations were observed in older RA patients, in patients with longer duration of RA disease and in those who had been treated with methotrexate. Also positive correlation was found between RA SF concentrations and SF leukocyte numbers (r = 0.497, p < 0.05)., Conclusions: The SF and serum CCL2/MCP-1 concentrations are significantly greater in RA than in OA and in hda-RA than in mda-RA; increased SF over serum concentrations suggest that CCL2/MCP-1 is mainly produced locally by activated cells where it may exacerbate and sustain inflammation by attracting proinflammatory leukocytes, predominantly monocytes (Tab. 1, Fig. 2, Ref. 50). Full Text (Free, PDF) www.bmj.sk.

The concentrations of alpha 1-acid glycoprotein (alpha 1-antitrypsin (alpha 1-AT), ceruloplasmin (Cp) and alpha 2-macroglobulin (alpha 2-MG) in serum and in knee joint synovial fluid of patients suffering from rheumatoid arthritis (RA) and osteoarthritis (OA) were determined and apparent synovial permeability (SP) to each protein calculated. The results showed that the rheumatoid synovia were significantly more permeable (P < 0.001) than the osteoarthritic synovia. Cp and alpha 2-MG showed the greatest average increase in apparent SP, about five times the values for OA joints. Apparent SP reflected disease activity rather well, since the patients with the more active disease had the highest values, six times that of the OA values. Although the values for the small proteins alpha 1-AGP and alpha 1-AT were greater in RA joints, more intense inflammation resulted in a greater increase in apparent SP to larger proteins, so that the apparent SP for alpha 2-MG and Cp are more reliable for evaluating disease activity. Apparent SP as determined by this and previous studies appeared to be a much more accurate and sensitive measure than the synovial fluid/plasma protein concentration ratio. Knowledge of the apparent SP could be a useful parameter in evaluating synovitis since the exudative flare-ups usually parallel the intensity of the inflammation.

By determining the total activity of total lactate dehydrogenase (LDH-T) and its isoenzymes in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteo-arthritis (OA) we demonstrated in RA serum increased (p less than 0.02) activity of hepatic LDH (LDH-H) and a shift of the LDH isoenzymatic profile towards the M forms; in rheumatoid SF increased (p less than 0.001) activity of the total LDH-T and LDH-H which makes possible the use of these markers of inflammation in assessing RA activity. Values for LDH-T and LDH-H of 400-700 U/l and 300-500 U/l, respectively, correspond to moderate disease activity, while values exceeding 750 U/l and 550 U/l, respectively, correspond to high RA activity. The anaerobic isoenzymatic distribution of LDH in rheumatoid SF results in a significant (p less than 0.001) decrease in LDH1 and LDH2 and an increase (p less than 0.001) in LDH4 and LDH5.

Articular cartilage fragments were obtained from four femoral heads and one femoral condyle, resected in five patients undergoing prosthetic surgery for rapidly destructive arthropathy (RDA) and from one normal femoral head and one normal femoral condyle resected at autopsy. The cartilage fragments were labelled in vitro with 35SO4 and newly-synthesized proteoglycans, (35S-PGs) were then extracted with 4 M guanidinium hydrochloride (GuHCl) and analyzed. In three cases a much greater and in one case a significantly increased proportion of small 35S-PGs enriched in dermatan sulfate (DS) was demonstrated in diseased tissues in comparison with control samples. These DS 35S-PGs were completely unable to interact with hyaluronan (HA) and had longer glycosamino-glycan (GAG) side chains than large 35S-PGs. Also, large 35S-PGs extracted from diseased tissue interacted poorly under associative conditions with exogenous HA when this was added to the crude extract. However, they interacted much better following the addition of exogenous HA to the purified high density proteoglycans. This suggests the presence of an inhibitor of PG-HA interaction in the crude extract which is lost during PG purification. The synthesis of an abnormally large proportion of small PGs by articular chondrocytes and impaired aggregation of large PGs may account for the accelerated destruction of articular cartilage in this condition.

Cell and clonal density, lacunar and clonal diameters, and mean number of cells per single clone were studied in human femoral condylar cartilage of normal and osteoarthrotic joints. The values were related to the age of the subjects, the sampling site within the joints, and the depth from the articular surface. Cell density in every zone of both normal and diseased tissue decreased with increasing distance from the surface and increasing age. Cell density was significantly lower in age-matched osteoarthritic articular cartilage with an intact surface than in that of normal joints. The age-related decrease in the cell density accompanied an increase in the density of empty lacunae. The density of Alcian blue-stained cells, which actively synthesize proteoglycans as demonstrated by histoautoradiography, diminished with advancing age in all zones of articular cartilage. The percentage of these cells consistently decreased in the superficial and increased in the deep layers of the tissue in both normal and osteoarthritic joints. The clonal density was higher in the nonweight-bearing than in weight-bearing areas, and it increased with age, whereas the mean clone diameter and clonal cell number decreased.

Joint lesions were induced by implantation of a rigid piece of polyethylene sutured under the patella and quadriceps tendon of the rabbit's right knee. Compared to the left sham-operated knee, follow-up studies revealed progressive changes that consisted of early and transient synovial hyperemia and proliferation and late osteoarthritis. By day 7 after surgery, soft synovial-like tissue proliferated around the implant and the articular margins of the femoral trochlea indicating primitive "osteophytic" protuberances (synoviophytes). By day 15 after surgery, the synoviophytes had acquired a more solid consistency and were composed mostly of fibrocartilage covered by a fibro-cellular synovial lining (chondrophytes). By that time, this tissue was invaded with vascular channels; signs of ossification were already present in the deepest layer adjacent to bone. Between the 2nd and 12th weeks, this fibro-cartilaginous tissue, except for the surface fibrous or fibrocartilaginous layer, was progressively replaced by immature bone (osteophyte). Secondary bone remodeling started soon after the first lamellae of immature bone were deposited. Complete integration of the osteophyte into the distal femur occurred during the 2nd and 3rd month.

Implantation of a sterile rigid sheet of polyethylene into the right patellofemoral rabbit joint caused changes that resemble those found in human osteoarthritis. Initial synovial proliferation resulted in the isolation of the implant. Marginal osteophytes developed from soft cellular tissue which later underwent chondrification and finally became ossified. Articular cartilage under the area in contact with the implant showed early cell necrosis and diffuse loss of metachromasia. Focal superficial fibrillation followed and later developed into deep erosions and bone exposure. The first clefts appeared tangentially to the surface within an acellular electron-dense material. In spite of numerous mitotic divisions of viable chondrocytes, mainly in clusters or clones, cell density progressively decreased in every layer of articular cartilage beneath the implant. The present study suggests that necrosis of chondrocytes, and the later failure of viable cells to respond adequately to the altered environment, can lead to cartilage fibrillation and then to more severe lesions.

The cell density and incorporation of 35SO4 and 3H-glycine into human articular cartilage from 8 osteoarthrotic and 7 normal (subcapital fracture) femoral heads were studied. It was found that osteoarthrotic cartilage incorporates on a per cell basis about twice as much 35SO4 and 2--5 times as much 3H-glycine as normal cartilage. There was no relationship between the intensity of incorporation and either the location of the cartilage (weight-bearing versus non weight-bearing areas) in normal cartilage or the degree of damage (normal-like, fibrillated, and ulcerated) in osteoarthrotic articular cartilage. In the latter tissue the increased synthetic capacity of the cells seems to be a diffuse rather than a localised process, for it was also found in cartilage from peripheral osteophytes. Histo-autoradiographic studies showed that the osteoarthrotic chondrocytes are metabolically hyperactive all over the femoral head, including wedge-shaped margins of the zone of exposed bone. These results support the hypothesis that much of the articular cartilage from osteoarthrotic femoral heads is of an immature chondroblastic type. It is suggested that de-novo synthesis of articular cartilage occurs during the process of regional remodelling of the femoral head, which would account for the observed hyperactivity.

The authors studied the cellular density (number of cells per mm2) of cartilage taken from the femoral condyles of 46 cadavers (73 knees). In each case, the cartilage was taken from the summit of the condyle and, in 46 joints (27 subjects), a sample was also taken from the posterior surface (non weight-bearing zones). The fragments of non-calcified cartilage were sectioned with a cryostat and the sections (10 micrometers) were stained with hematein-eosin and solid red-Alcian blue. This study demonstrates: 1) a decrease in the cellular density of fissured cartilage compared to normal cartilage; this decrease appears to be proportional to the degree of fibrillation; 2) a decrease in the cellular density of apparently normal cartilage from arthrotic joints compared with normal cartilage from healthy joints; 3) with the age of the subjects, an increase in the density of the clones (number of clones per mm2) and the density of clonal cells (number of clonal cells per mm2) together with a decrease in the mean number of chondrocytes per clone. In fissured cartilage, the density of the clones, the density of the clonal cells and the number of chondrocytes per clone are slightly higher on the posterior surface of the condyles than on the summit of the condyles. These results emphasise the importance of the role that might be played by cellular phenomena in the mechanisms of deterioration of cartilage with aging and with arthrosis.

The joint tissues (synovium, articular cartilage and bone), respond rapidly and consistently to the presence of a piece of polypropylene surgically implanted into the Rabbit knee joint. In the contact of a foreign body, a synovium proliferates in an attempt to isolate and exclude the intruder from the joint cavity. The articular cartilage degenerates at the sites of maximal pressure. Its superficial layer undergoes cell necrosis and fibrillation and is progressively destroyed in the process of mechanical grinding. At the sites of lower pressure, the chondrocytes proliferate and form the metabolically hyperactive clones which have increased capacity to incorporate tritiated thymidine and radioactive sulfate. The glycosaminoglycan content of articular cartilage, compared to the shamoperated control side, rapidly decreases after operation as suggested by a loss of metachromatic staining and lower per unit weight concentration of uronic acid and hexosamine. In addition to the above changes, the osteophytes quickly develop at the articular margins from the proliferating synovial tissue while underlying bone become thicker and eburnated. These foreign body induced changes in articular morphology and metabolism resemble closely those observed in osteoarthrosis. The present model therefore may prove useful in studying the latter condition.

Although the frequency and severity of osteo-arthrosis regularly increase after the age of 50 years, individual's age does not seem to be a causal factor of this disorder. Indeed, osteoarthrosis does not affect all age individuals and not all joints are involved at the time. Various etiological factors (traumatisms, joint malformations and preexisting disorders, overuse of joints, etc.) are usually identified. Joint lesions in osteo-arthrosis are not those characteristic of senile involution, but rather represent proliferative reparative processes. Therefore, old age may act as one of the risk factors, which favors a development of osteo-arthrosis if others, more specific, etiological factors are present.