Publisher Summary This chapter discusses the general composition of cartilage, glycosaminoglycans, keratan sulfate, hyaluronic acid, and proteoglycans. Several types of connective tissue represented by ligaments, tendons, synovial membrane, and cartilage are found in diarthrodial joints. However, with the exception of cartilage, little is known about the ground substance of these tissues. Cartilage is an avascular tissue in which the cells are sparsely distributed in a stiff matrix. It is mechanically perhaps the most important tissue of diarthrodial joints and is well adapted to perform an exacting mechanical function, in having to withstand very high repetitive compressive loads that generate localized stresses. The water content of articular cartilage is about 65–75% and is highest near the joint surface of normal femoral condyles. The water content of patellar cartilage is similar. Although the content of water is high, it is precisely the presence of water in conjunction with proteoglycans and collagen that makes cartilage tough and resilient. Collagen accounts for about half the dry weight of human adult articular cartilage.

The Chemistry of the Ground Substance of Joint Cartilage

The influence of joint inflammation on patellar hyaline articular cartilage was studied in mice Antigen-induced and zymosan-induced arthritis were used as models for immunologically and non-immunologically induced joint inflammation The contribution of newly formed proteoglycan to the cartilage proteoglycan content, as measured by labelling of the cartilage after iv administration of 35S-sulphate, was decreased in parallel with the severity of inflammation during both zymosan-induced and antigen-induced arthritis The decreased 35S content of the cartilage was due to inhibition of synthesis rather than breakdown of newly synthesized proteoglycan, since no accelerated release of 35S from arthritic cartilage could be demonstrated in vitro Antigen-induced arthritis was associated with progressive chondrocyte damage Loss of chondrocytes was consistently found in the central part of the patella, without nearby presence of pannus It would appear that, in addition to enzymatic breakdown of cartilage, other phenomena are important in cartilage destruction: inhibition of proteoglycan synthesis and chondrocyte death, apparently unrelated to pannus formation

Antigen-induced and zymosan-induced arthritis in mice: studies on in vivo cartilage proteoglycan synthesis and chondrocyte death.

An easy method of quantitating articular cartilage chondrocyte function in mice is described, using a defined and anatomically intact cartilage structure, the patella. To avoid damage to the cartilage before incubation, 35S incorporation studies were performed leaving the patellae surrounded by a minimal area of non-cartilaginous connective tissue. The patellae were then punched out so that the 35S activity incorporated into the cartilage could be measured. Incorporation of 35S was almost completely blocked by 0.1 mM cycloheximide. Patellar cartilage from left and right knee joints of individual mice shows identical incorporation of 35S, as indicated by a right/left ratio of 1.01 in vitro and 0.99 in vivo, respectively. 35S incorporation values of patellae of mice of different ages do show considerable variation, but within properly age-matched groups of mice the incorporation values are comparable. A known suppressive effect of acute joint inflammation on proteoglycan synthesis was reliably quantitated in the zymosan-induced arthritis model, as indicated by 39% in vitro and 35% in vivo inhibition of 35S incorporation. The patella assay can be used for quantitative measurement of chondrocyte metabolism in normal and pharmacologically altered cartilage.

The mouse patella assay

Juxtaarticular bone loss in experimental inflammatory arthritis.

An arthritis was induced in rabbits immunized with human serum albumin by injection of antigen into the hind knee joint. Histological changes in the synovial membrane and an increase in polymorphonuclear granulocytes in the synovial fluid indicated an inflammatory response similar to that described with fibrin as antigen (1). The arthritis was accompanied by no significant change in the collagen content, but a marked decrease in the proteoglycan content of the cartilage was noted. Cartilage from inflamed joints generally exhibited a decreased ability to synthesize proteoglycan in vitro.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780210611

Antigen‐induced arthritis. decreased proteoglycan content and inhibition of proteoglycan synthesis in articular cartilage

A localized inflammatory response was initiated by both single and repeated injections of carrageenin into femorotibial joints. Histologic changes were observed 24 hours after a single intraarticular injection, and an inhibition in the in vitro rate of proteoglycan synthesis was detected 72 hours after the injection. This inhibition was relieved in vitro by the addition of beta-D-xyloside, an exogenous initiator of glycosaminoglycan biosynthesis. Following repeated carrageenin injections, most cells appeared to be dead on histologic examination and no in vitro proteoglycan synthesis could be detected; nor could any stimulation be achieved by adding exyloside.

D. J. Carmichael

Papers

Carrageenin‐induced arthritis