Distribution and binding of glycosaminoglycan polysulfate to intervertebral disc, knee joint articular cartilage and meniscus.
The relative incorporation of 3H-Glycosaminoglycan polysulfate (3H-GP, Arteparon) into rabbit knee joint articular cartilage, patella cartilage, meniscus and intervertebral disc tissues was determined at 1, 2, 4 and 8 d after intramuscular administration (60 muCi/kg, 400 micrograms/kg). The distribution of the drug within these tissues was also examined autoradiographically. The highest uptake of 3H-GP occurred in the menisci and was observed to be largely localised about collagen fibres on the outer periphery of these tissues. Over the eight day period, the level present declined to approximately 50% of that present on day one. The level of drug attained in articular and patella cartilages was approximately 20-25% of that in the meniscus. It was uniformly dispersed and remained fairly constant over the eight day period. Of greatest interest was the finding for the disc, where the highest level of labelling, which occurred on day two, was comparable to the knee joint hyaline cartilages and was associated with the collagenous lamella structure of the outer annulus fibrosus. After day two, the level of drug in these areas declined, accompanied by an accumulation in the nucleus pulposus. Using an ion exchange assay technique, and gel permeation chromatography of 4M guanidine hydrochloride extracts of these connective tissues, binding of 3H-GP to proteoglycans, collagen and non-collagenous proteins, was demonstrated; the latter component representing the major drug binding species. It is suggested that localisation of the drug within these connective tissues may be beneficial in protecting their matrix components against enzymatic degradation in the pathological state.
D000818:Animals; D001345:Autoradiography; D002358:Cartilage, Articular / Q000378:metabolism*; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism*; D007719:Knee Joint / Q000378:metabolism*; D008592:Menisci, Tibial / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D013997:Time Factors; D014018:Tissue Distribution
D006025:Glycosaminoglycans; C013786:A73025; D003094:Collagen