Meniscus is more susceptible than cartilage to catabolic and anti-anabolic effects of adipokines

Abstract

Objective This study compared the effects on cartilage and meniscus matrix catabolism and biosynthesis of several adipokines implicated in osteoarthritis. Design Cartilage and meniscus explants were cultured for 1 or 9 days in serum-free medium alone or with 0.02, 0.2, or 2μg/ml of leptin, visfatin, adiponectin, or resistin. Media were supplemented with 3H-proline or 35S-sodium sulfate to evaluate protein and sulfated glycosaminoglycan (sGAG) accumulation on the last day of culture. Explants were assayed for radiolabel, sGAG, and DNA contents. Cultured media were assayed for sGAG, nitrite and lactate dehydrogenase. Results Cartilage tissue was minimally affected by adipokines, with only the highest resistin dose increasing sGAG release and nitrite production compared to controls. In sharp contrast, meniscus tissue was responsive to several adipokines, with elevated sGAG and nitrite release following treatment with resistin, leptin, or visfatin. Cartilage sGAG content was unaltered by adipokine treatment whereas meniscal sGAG content significantly decreased with resistin dosage. Protein (3H) incorporation was unaffected by adipokine treatment in both tissues. sGAG (35S) incorporation did not significantly vary with adipokine treatment in cartilage but was inhibited by treatment with leptin, visfatin, and resistin in meniscus. Conclusion Our results indicate that meniscal tissue is more susceptible to adipokine-stimulated catabolism than is cartilage. Resistin had the strongest effect of the adipokines tested, inducing sGAG release in both tissues and depleting sGAG content in meniscus. These results suggest that increased adipokine levels due to obesity or joint injury may alter the mechanical integrity of the knee joint through biological pathways.

Co-culture with infrapatellar fat pad differentially stimulates proteoglycan synthesis and accumulation in cartilage and meniscus tissues

“…Consistent with previous observations of juvenile tissues (30), nitrite release was greater in cartilage than meniscus, perhaps due to greater cellularity of cartilage tissue (as evidenced by greater DNA content). While cumulative nitrite release was greater in co-cultured meniscus than in meniscus cultured alone, the nitrite release rate was unaffected.…”

“…Adipose tissues can also produce a wide range of signaling molecules, and considerable recent interest has focused on the effects of fat-secreted factors on other tissues. In studies on the isolated effects of individual adipokines that can be produced by IFP, we found that several adipokines (most notably resistin) stimulated catabolic and anti-anabolic responses in cartilage tissues, with meniscus exhibiting greater sensitivity than articular cartilage (30). In contrast, the current co-culture study found that both cartilage and meniscus tissues displayed a modest anti-catabolic response to co-culture with fat (lower MMP-2 production) and cartilage but not meniscus exhibited a substantial anabolic response.…”

Adipokine Contribution to the Pathogenesis of Osteoarthritis

“…It has a positive correlation with obesity, insulin resistance, and chronic inflammation [153, 170] (Figures 1(a) and 1(b)). In murine models, cartilage and in human primary chondrocytes resistin was also found to induce MMP13, ADAMTS4, PGE 2 , TNF- α , and IL-8 (Figure 5 and Table 1) [171].…”

Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells

“…A recent study showed that increase in body mass index (BMI) negatively regulated gene transcripts associated with extracellular matrix in human meniscus (6). In addition, meniscus was more susceptible than articular cartilage to catabolic effects of adipokines (7). These studies suggest that meniscus could be a primary tissue affected in obesity-linked OA.…”