ABSTRACT
OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of articular cartilage. While macroscale degradation of the cartilage extracellular matrix (ECM) has been extensively studied, microscale changes in the chondrocyte pericellular matrix (PCM) and immediate microenvironment with OA are not fully understood. The objective of this study was to quantify osteoarthritic changes in the micromechanical properties of the ECM and PCM of human articular cartilage in situ using atomic force microscopy (AFM). METHOD: AFM elastic mapping was performed on cryosections of human cartilage harvested from both condyles of macroscopically normal and osteoarthritic knee joints. This method was used to test the hypotheses that both ECM and PCM regions exhibit a loss of mechanical properties with OA and that the size of the PCM is enlarged in OA cartilage as compared to normal tissue. RESULTS: Significant decreases were observed in both ECM and PCM moduli of 45% and 30%, respectively, on the medial condyle of OA knee joints as compared to cartilage from macroscopically normal joints. Enlargement of the PCM, as measured biomechanically, was also observed in medial condyle OA cartilage, reflecting the underlying distribution of type VI collagen in the region. No significant differences were observed in elastic moduli or their spatial distribution on the lateral condyle between normal and OA joints. CONCLUSION: Our findings provide new evidence of significant site-specific degenerative changes in the chondrocyte micromechanical environment with OA.
Subject(s)
Cartilage, Articular/ultrastructure , Chondrocytes/ultrastructure , Extracellular Matrix/ultrastructure , Osteoarthritis, Knee/pathology , Aged , Aged, 80 and over , Cartilage, Articular/metabolism , Case-Control Studies , Collagen Type VI/metabolism , Elastic Modulus , Extracellular Matrix/metabolism , Female , Humans , Immunohistochemistry , Male , Microscopy, Atomic Force , Microscopy, Scanning Probe , Middle Aged , Osteoarthritis, Knee/metabolismABSTRACT
OBJECTIVE: Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meniscal repair interfaces. While mechanical stress and IL-1 modulate meniscal biosynthesis and degradation, the effects of dynamic loading on meniscal repair are unknown. The purpose of this study was to determine the effects of mechanical compression on meniscal repair under normal and inflammatory conditions. EXPERIMENTAL DESIGN: Explants were harvested from porcine medial menisci. To simulate a full-thickness defect, a central core was removed and reinserted. Explants were loaded for 4h/day at 1 Hz and 0%-26% strain for 14 days in the presence of 0 or 100 pg/mL of IL-1. Media were assessed for matrix metalloproteinase (MMP) activity, aggrecanase activity, sulfated glycosaminoglycan (S-GAG) release, and nitric oxide (NO) production. After 14 days, biomechanical testing and histological analyses were performed. RESULTS: IL-1 increased MMP activity, S-GAG release, and NO production, while decreasing the shear strength and tissue repair in the interface. Dynamic loading antagonized IL-1-mediated inhibition of repair at all strain amplitudes. Neither IL-1 treatment nor strain altered aggrecanase activity. Additionally, strain alone did not alter meniscal healing, except at the highest strain magnitude (26%), a level that enhanced the strength of repair. CONCLUSIONS: Dynamic loading blocked the catabolic effects of IL-1 on meniscal repair, suggesting that joint loading through physical therapy may be beneficial in promoting healing of meniscal lesions under inflammatory conditions.
