Development and Reversal of a Proteoglycan Aggregation Defect In Normal Canine Knee Cartilage After Immobilization

Abstract

Healthy adult dogs were studied for a defect in proteoglycan aggregation by immobilizing one limb for varying periods of time. Immobilization for 6 days resulted in a 41% reduction in proteoglycan synthesis by articular cartilage from the restrained knee compared with the contralateral control knee. After 3 weeks of immobilization, proteoglycan aggregation was no longer demonstrable in cartilage from the constrained limb. The aggregation defect was rapidly reversible and aggregates were again normal size 2 weeks after removal of a cast that had been worn for 6 weeks.In normal articular cartilage most of the proteoglycans (PG) exist in large aggregates that are noncovalently linked to hyaluronic acid (HA) (1). In osteoarthritis (OA) an aggregation defect exists within the tissue, since a greater than normal proportion of the PGs is not aggregated and aggregates which are present tend to be smaller than normal (2-5).Aggregation defects similar to those of OA in

Effect of link protein concentration on articular cartilage proteoglycan aggregation

“…Noncovalent association, or aggregation, of monomers, hyaluronan, and link proteins to form proteoglycan aggregates helps to stabilize aggrecans within the matrix and contributes to the organization of the matrix (12). The loss of aggregates or a decrease in their size is among the earliest, if not the earliest, changes in articular cartilage in aging, joint degeneration, and joint immobilization (5,7,10, 13,18,(20)(21)(22)(23)26), which suggests that proteoglycan aggregation and the stability of aggregates are critical for normal structure and function of cartilage.…”

“…Concentrations of more than 10% link protein led to the formation of superaggregates with sedimentation velocities of greater than 100 S but decreased aggregate stability. These observations may have implications for the changes in proteoglycan aggregation seen in articular cartilage with joint degeneration, joint immobilization, and aging (5,7,10,(18)(19)(20)(21)(22)(23). A decline in functional link protein concentration below 6%, and especially below 4%.…”

“…Noncovalent association, or aggregation, of monomers, hyaluronan, and link proteins to form proteoglycan aggregates helps to stabilize aggrecans within the matrix and contributes to the organization of the matrix (12). The loss of aggregates or a decrease in their size is among the earliest, if not the earliest, changes in articular cartilage in aging, joint degeneration, and joint immobilization (5,7,10, 13,18,(20)(21)(22)(23)26), which suggests that proteoglycan aggregation and the stability of aggregates are critical for normal structure and function of cartilage.The factors that control aggregation and aggregate stability remain poorly understood; however, previous work showed that link proteins may have an impor- Received February 7,1995; accepted September 11,1995 tant role (11,15,17,25). A recent study of bovine nasal proteoglycans showed that increasing the ratio of link protein to aggrecan decreased the spacing between aggrecans and increased the number of aggrecans per aggregate, as measured by electron microscopy (14).…”

Histopathological Changes in Knee Joint Components after Spinal Cord Injury in Rats

“…Joint immobility may be caused by cast immobilization (CI), external fixation, or after neurological paralysis. Variable and somewhat controversial morphological alterations in the knee joint components resulting from immobilization have been described, and the changes include, increased thickness and decreased area of elastic fibers of the joint capsule 1) , increased surface irregularity [2][3][4] , increased or decreased or unchanged thickness of cartilage [5][6][7][8] , decreased synovial intima length 9) , augmentation of levels of type I c o l l a g e n i n t h e s y n o v i a l i n t i m a 1 0 ) , s y n o v i o c y t e proliferation 11,12) and decreased cross-sectional areas of myocytes 13) .…”

Cartilage response to mechanical force in high‐density chondrocyte cultures

“…The initial in vivo response of articular cartilage to repetitive trauma is enhanced matrix production without cell proliferation (17), whereas a decrease in loading provokes degenerative changes in the articular cartilage (18,19). This study reports the in vitro response of high-density chondrocyte cultures to intermittent compression.…”