Sulphate (35SO4) Uptake by Chondrocytes in Relation to Histological Changes in Osteo-Arthritic Human Articular Cartilage

Abstract

Quantitative studies of sulphate uptake by the cells of human cartilage (McElligott and Collins, 1960) have shown that chondrocyte activity increases in articular cartilage as age advances, while it decreases in costal cartilage. A considerably enhanced activity of articular over costal cartilage cells was recorded in cases where there was nakedeye evidence of destruction and fibrillation of the articular cartilage. We postulated a possible relationship between the increased sulphate utilization of ageing articular cartilage, the degree of osteo-arthritis, and the peculiar rearrangement and grouping of chondrocytes that are known to occur in these conditions. In order to investigate this, a large number of autoradiographs of cartilage incubated with labelled sulphate have been prepared and studied side by side with parallel sections stained by various methods including those that demonstrate mucopolysaccharides. It is the results of these studies that we now report. Material and MethodsA patella was removed at each of 34 necropsies from persons ranging in age from 4 to 83 years. Specimens were processed as soon as possible after removal and in all cases within 2 hours. During this delay the specimens were stored at 40 C. in the incubation medium, a procedure that reduces the rate of loss of chondrocyte activity. The intervals between death and autopsy and between the collection of the specimen and its processing were carefully noted.Preparation of Specimens. The patellae were inspected and changes of osteo-arthritis, if present, were graded 0-4 according to the classification proposed by Collins (1949, p. 76). Blocks of cartilage down to the bone were removed from the complete transverse diameter of the patellae and processed for quantitative measurement of sulphate fixation in 31 cases, as previously described (McElligott and Collins, 1960).Another block of cartilage with its subjacent bone was then cut from the specimen; this second block of cartilage adjoining that removed for radiochemical assay was used for the histological procedures to be described. The cut surfaces of the cartilage were then shaved with a razor so as to produce a block of the complete depth of the articular cartilage 1 mm. or less in thickness resting on a broader supporting block of the underlying bone, since thicknesses of cartilage greater than 1 mm. impair the uptake of "5SO4 (Bostrom and MaInsson, 1953). Incubation Medium.-The medium used for incubating the specimens and in which they were transported was that described by Kodicek and Loewi (1955 Layton (1950) reports that higher uptake of radioactive sulphate occurs where carrier is omitted.Radiochemical Technique.-The quantitative procedure, based on the methods fully set out by Layton (1949Layton ( , 1950 and by Kodicek and Loewi (1955), has been previously described (McElligott and Collins, 1960). In the preparation of autoradiographs the blocks of cartilage and bone were incubated in 10 ml. medium at 37°C. in a water bath, in flasks mounted in a mechanical rocker. Approxima...

Chondrons from articular cartilage. III. Morphologic changes in the cellular microenvironment of chondrons isolated from osteoarthritic cartilage

“…The histologic results presented are consistent with those found in numerous studies of human and experimental OA (20)(21)(22)(23)(24)(25)(26)(27). They show a general loss of intercellular matrix staining, but persistence of a strong pericellular reaction around most chondrocytes and cell clusters.…”

“…However, despite their routine description in published reports, relatively little is known of their formation or function. Previous studies have demonstrated enhanced sulfate incorporation by chondrocyte clusters in fibrillated patellae, and this was related to the rate of chondrocyte proliferation (21,44). While chondrocytes in normal cartilage are generally considered to be mitotically dormant, convincing metabolic (35,47,50) and autoradiographic (45,46,48,49) evidence has shown that chondrocytes can switch to a reactive mitotic proliferation under traumatic or degenerative conditions.…”

“…It is characterized in both spontaneous and experimentally induced disease by marked alterations in matrix histochemistry (20)(21)(22)(23)(24)(25)(26)(27) and ultrastructure (28-34), biochemical composition (3541), and cellular metabolism (21,35,(42)(43)(44). Variable rates of chondrocyte necrosis and reactive mitotic proliferation have also been reported (35,(45)(46)(47)(48)(49)(50).…”

“…Silberberg et a1 (20) argued that biochemical and/or biomechanical changes in the intercellular matrix might compromise "the restraining powers which it usually exerts on cell growth," releasing the dormant growth potential of the chondrocyte (21). Mankin and Lippiello (35) subsequently speculated that the microenvironment around each chondrocyte could stimulate chondrocyte metabolism and proliferation, possibly in a negative feedback response to reduced levels of matrix proteoglycans.…”

In vitro rabbit articular cartilage organ model I. Morphology and glycosaminoglycan metabolism

“…DISCUSSION An in vitro adult rabbit articular cartilage organ model has been reported. Dziewiatkowski and others (1)(2)(3)(4)(5)13,14) have clearly shown that 90% plus of s 5 S 0 , is incorporated into glycosaminoglycans and that its incorporation is related to the rate of synthesis. By utilizing this technique we have shown that the articular cartilage slices and floating plugs have the property of a constant rate of 35S0, incorporation into glycosaminoglycans from day 7 to day 14.…”