Large aggregating and small leucine‐rich proteoglycans are degraded by different pathways and at different rates in tendon

Abstract

S]sulfate lost to the medium and retained in the matrix was determined for each day in culture. It was shown that the rate of catabolism of radiolabelled small proteoglycans (decorin and biglycan) was significantly slower (T ½ > 20 days) compared with the radiolabelled large proteoglycans (aggrecan and versican) that were rapidly lost from the tissue (T ½ 2 days). Both the small and large newly synthesized proteoglycans were lost from the matrix with either intact or proteolytically modified core proteins. When explant cultures of tendon were maintained either at 4°C or in the presence of the lysosomotrophic 2 agent ammonium chloride, inhibition of the cellular catabolic pathway for small proteoglycans was demonstrated indicating the involvement of cellular activity and lysosomes in the catabolism of small proteoglycans. It was estimated from these studies that approximately 60% of the radiolabelled small proteoglycans that were lost from the tissue were degraded by the intracellular pathway present in tendon cells. This work shows that the pathways of catabolism for large aggregating and small leucine-rich proteoglycans are different in tendon and this may reflect the roles that these two populations of proteoglycans play in the maintenance of the extracellular matrix of tendon.

A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs

“…Certainly, biglycan and fibromodulin are fragmented in models of IVD degeneration and osteoarthritis (OA) [19,35] and in articular cartilage from total knee and hip replacement patients and from menisci of OA joints [17]. SLRPs are also extensively fragmented in pathological tendon and ligament [10,24,25]. Fragmentation of SLRPs may alter their function significantly, possibly rendering them more potent at stimulating inflammation.…”

Sulfated polysaccharides inhibit the catabolism and loss of both large and small proteoglycans in explant cultures of tendon

“…These samples were subjected to size-exclusion chromatography on a column of Sepharose CL-4B eluted under dissociative conditions as described in the Experimental procedures (data not shown). From this, the percentage of 35 S-labeled large and small proteoglycans remaining in the matrix at various times after incubation of tendon with [ 35 S]sulfate was determined as previously described [10]. S-labeled large proteoglycans remaining in the matrix by day 10 of culture was 45%.…”

“…This further indicates that these highly sulfated agents inhibit the loss of Culture medium was collected daily and the tissue extracted at the end of the culture period with 4 m GnHCl followed by 0.5 m NaOH as described in the Experimental procedures. Both medium and tissue extract samples were analyzed for the presence of 35 S-labeled macromolecules and free [ ]sulfate in the medium throughout the culture period results from intracellular degradation of small proteoglycans [10]. Figure 4A shows that the rate of [ ]sulfate in the culture medium by 5 and 11%, respectively.…”

“…The large proteoglycans aggrecan and versican are found in similar proportions in tendon, and together make up almost 20% of the total proteoglycan content of the tissue [5]. These proteoglycans can bind to hyaluronan and form hydrated aggregates within the extracellular matrix or interact with other matrix macromolecules and contribute to the organization of the extracellular matrix [7].We have previously shown in both cartilage and fibrous connective tissues such as tendon and ligament that the loss of newly synthesized large proteoglycans from the matrix occurs at a faster rate than that of small proteoglycans [8][9][10]. In arthritic diseases, the large proteoglycans are one of the first matrix components to be degraded and lost from the articular cartilage and this is associated with impairment of the biomechanical function of the tissue [11].…”

“…In contrast, the degradation of small proteoglycans in cartilage, ligament and tendon appears to occur at a slower rate, even in the presence of catabolic agents [8,10,18]. This may suggest that the interaction of the small proteoglycans with the surface of the collagen fibrils may protect these proteoglycans from proteolysis during the early phases of connective tissue degradation [18].…”