Degeneration affects the structure-function relationship of the human meniscus

To investigate whether alterations in the structure-function relationship of osteoarthritic menisci are associated with the production of catabolic and inflammatory mediators, including the terminal complement complex (C5b-9). Twenty-four human knee joint menisci were equally assigned to mild and severe degeneration groups. Tissue explants underwent pull-to-failure and stress-relaxation testing. Biochemical assays quantified DNA, sulfated glycosaminoglycan (sGAG), and collagen content. Immunohistochemistry assessed collagen types I/II, aggrecan, matrix metalloproteinase (MMP)-3, interleukin (IL)-6, C5b-9, and vascular endothelial growth factor production. Spearman correlation coefficients (SCCs) were calculated to investigate associations between outcome measures. Degeneration-associated changes were mainly observed in medial menisci. Elastic modulus and tensile strength were significantly lower in severely compared to mildly degenerated specimens (mean difference: 13.39 [95% CI: 2.38, 24.40] MPa and 2.54 [0.60, 4.49] MPa, respectively). Degeneration significantly increased permeability (-10.17 [-15.20, -5.20] ×10-15m4/Ns) and sGAG (-16.57 [-30.90, -2.19]), whereas collagen decreased by 116.00 [51.20, 181.00], without affecting collagen types I/II. Severely degenerated menisci produced more MMP-3 (-12.70 [-22.70, -2.70]), IL-6 (-7.76 [-14.16, -1.37]), and C5b-9 (-12.47 [-20.70, -4.25]) than mildly degenerated specimens. In mild degeneration, collagen correlated positively with failure strain (SCC 0.72 [0.25, 0.92]) but became a negative association in the severe degeneration group (SCC -0.37 [-0.81, 0.34]). Correlation analyses between functional, structural, and inflammation-related parameters revealed distinct meniscal phenotypes associated with degeneration severity. Positive correlations in mildly degenerated menisci shifted to negative correlations in severely degenerated specimen (and vice versa), highlighting the complexity of meniscal degeneration during osteoarthritis progression.