Cultured human ankle and knee cartilage differ in susceptibility to damage mediated by fibronectin fragments

Abstract

According to numerous cadaveric, radiographic, and clinical studies, ankle and knee joints differ in susceptibility to osteoarthritis. To test for biochemical differences in susceptibility to damage, a chondrocytic chondrolysis system has been utilized. In this system, fibronectin fragments are added to cultured cartilage explants, resulting in enhanced release of catabolic cytokines, induction of matrix metalloproteinases, temporary suppression of proteoglycan synthesis, and consequently, severe loss of cartilage proteoglycan. We found that the addition of an amino-terminal thrombin-generated 29-kDa fibronectin fragment to cultured knee cartilage from 14 donors (average age: 53 years) usually caused a 30-50% decrease in proteoglycan content by day 7. However, of the ankle cartilage specimens examined from 21 donors (average age: 50 years), only three showed damage by day 7, one by day 14, and six by day 21, and 11 were not damaged until day 28. For eight of the donors (average age: 44 years), both knee and ankle cartilages were obtained: this allowed comparison between tissues from the same donor. The analysis showed that the ankle cartilage was much more refractory to damage than was the knee cartilage from the same donor. These data clearly show differences between ankle and knee cartilage in susceptibility to the fibronectin fragments and suggest the feasibility of use of these fragments for discerning differences in homeostasis of the ankle and knee cartilage.

Etiology of Ankle Osteoarthritis

“…This difference may be one of the main reasons for increased cartilage degeneration and the high rate of primary OA in the knee [9,41]. Although the ankle cartilage is thinner compared with knee or hip cartilage (ankle, 1.0-1.62 mm; knee, 1.69-2.55 mm; hip, 1.35-2.0 mm) [35], the ankle cartilage shows a higher compressive stiffness and proteoglycan density [41], lower matrix degradation [1], and less response to catabolic stimulations (as interleukin 1, fibronectin fragments) [5,15]. This fact of relative higher cartilage resistance might protect the ankle from degenerative changes leading to primary OA.…”

Composition and transport properties of human ankle and knee cartilage

“…Via diffusion, these cytokines may stimulate chondrocytes to produce more inflammatory mediators such as prostaglandin E2, nitric oxide, or matrix metalloproteinases (MMPs) that inhibit proteoglycan and collagen synthesis and promote extracellular matrix degradation. 18 For example, previous studies have shown a significantly lower catabolic response of ankle cartilage to IL-1, 17,18 or fibronectin fragments, 19 as compared to knee cartilage. This difference in cellular response may, in part reflect the lower partition coefficient of ankle cartilage, which would effectively reduce the interstitial concentration of such soluble mediators for an equivalent concentration in the external bathing solution or synovial fluid.…”

“…It should be noted, however, that the molecule used in this experiment was a linear 70-kDa dextran, whereas IL-1 and fibronectin fragments are 17.5-and 29-kDa molecules, respectively. 19,45 It remains to be determined whether the difference in partition would still be observed using smaller, globular molecules.…”

“…17,18 Ankle cartilage is more resistant than knee cartilage to the catabolic effects of fibronectin fragments. 19 Normal ankle cartilage does not express matrix metalloproteinase 8 (MMP-8) mRNA, an enzyme believed to play a role in matrix degradation. However, normal knee cartilage, as well as osteoarthritic ankle and knee cartilage do express MMP-8 mRNA.…”

Physical Diagnostics of Cartilage Degeneration

“…Ankle chondrocytes are less responsive than those of knee cartilages to catabolic mediators Section 2.2 64-such as interleukin-1 or fibronectin fragments, and have lower gene expression of certain matrix metalloproteinases (e.g., MMP-8) [41,42,97,119]. Since talar cartilage is thinner, the superficial zone comprises a higher proportion of the full thickness and thus may provide a protective layer more resistant to damage.…”