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A consideration of the permeability of cartilage to inorganic sulfate.

On the basis of an examination of autoradiograms of knee-joints fixed so as to remove chondroitin sulfate or inorganic sulfate, or to minimize the loss of both, it is suggested that the cartilage is permeable to inorganic sulfate in vivo and in vitro. In vivo and in vitro, almost as rapidly as it enters the cartilage, inorganic sulfate is utilized by the cells in the synthesis of chondroitin sulfate. The net result is a continuing low concentration of inorganic sulfate in the cartilage.

Cartilage↗

Estradiol reduces incorporation of radioactive sulfate into cartilage and aortas of rats.

Estradiol in large amounts reduces the incorporation of radioactive sulfate into cartilage and aortas of rats. This reduction becomes apparent within 3 days for cartilage and 3 weeks for aorta. The effect is not mediated through suppression of testosterone secretion and the hypophysis is not necessary for the effect to be demonstrated. The thoracic segment of aortas from normal rats incorporates more sulfate than does the abdominal segment and this difference is reduced following the administration of estradiol.

Animals↗

Metabolic effects of lathyrogenic agents on cartilage in vivo and in vitro.

The effects of lathyrogenic agents in vivo and in vitro are described, in respect to some biochemical indices of cartilage metabolism. Lathyrogenic agents in vivo inhibited the incorporation of radiosulfate into rat epiphyseal cartilage and the isolated chondroitin sulfate. No significant changes in hydroxyproline or hexosamine content of epiphyseal cartilage were found, but there was a marked increase in water content. The content of chondroitin sulfate, measured as uronic acid, was decreased. The importance of taking growth rate differences between control and experimental rats into account in assessing the effects of lathyrogenic agents in vivo is emphasized. In an in vitro system, utilizing fresh calf costal cartilage slices, the presence of low concentrations of lathyrogenic agents markedly affected various metabolic events. The incorporation into cartilage slices of sulfate-S(35), glucose-U-C(14), and glycine-1-C(14) was significantly depressed, as was the production of organic acids, including lactic acid. In general, these effects were more severe under anaerobic conditions. Glutamine restored the activities of the slices treated with lathyrogenic agents to control values obtained in the absence of either lathyrogen or glutamine.

Animals↗

Radioautographic studies of sulfate-sulfur (S35) metabolism in the articular cartilage and bone of suckling rats.

Fifteen minutes after intraperitoneal injection of sulfur-35 as sodium sulfate to 7-day-old rats the concentration of the isotope was highest in the cartilage at the epiphyseal-diaphyseal junction of long bones but was demonstrable throughout the entire epiphysis. Up to the 24th hour the pattern of deposition did not change as the concentration continued to increase. As centers of secondary ossification developed, there occurred in them an increased concentration of some form of sulfur, insoluble as the barium salt. This sulfur was probably derived from the cartilage which the center of secondary ossification replaced. Up to about the 30th minute after injection the sulfur-35 was deposited transitorily in a high concentration in discrete loci of the bone marrow. Excluding this transitory deposition, the highest concentration of the radioisotope in the bone marrow was seen in the specimens removed 24 hours after administration. In the bone shaft the sulfur-35, in a form which was insoluble in an alkaline solution of barium ions, was deposited diffusely up to the 24th hour after its administration. Thereafter, the radioisotope decreased in concentration in the middle portion of the bone shaft. However, the concentration of a similarly characterized sulfur-35-bearing component in the ends of the diaphysis continued to increase up to at least the 96th hour after injection.

Animals↗

The effect of ascorbic acid oxidation on the incorporation of sulfate by slices of calf costal cartilage.

A marked inhibition of the incorporation of S(35)-sulfate by normal calf costal cartilage was produced by potassium ascorbate in the presence of catalytic amounts of cupric ions. The effect of the various components of the ascorbic acid oxidizing system (potassium ascorbate, cupric ions, cuprous ions, hydrogen peroxide, dehydroascorbic acid) was investigated. The results of experiments in which hydrogen peroxide, catalase, or sodium azide were used singly or in combination suggest that the inhibition produced by the ascorbic acid oxidizing system is due, to a considerable extent, to the production of hydrogen peroxide. Dehydroascorbic acid was also found to inhibit the incorporation of S(35)-sulfate by cartilage slices. However, the gradual fall in pH which resulted from the addition of dehydroascorbic acid could account to a large extent for the inhibitory effect observed because the incorporation of S(35)-sulfate by cartilage slices decreases sharply as the pH is lowered. The incorporation of S(35)-sulfate by cartilage slices is inhibited also by increasing the concentration of phosphate.

Animals↗