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. 2013 Dec;21(12):1895-903.
doi: 10.1016/j.joca.2013.08.026. Epub 2013 Sep 8.

Micromechanical mapping of early osteoarthritic changes in the pericellular matrix of human articular cartilage

R E Wilusz  1 , S Zauscher, F Guilak
Affiliations

Micromechanical mapping of early osteoarthritic changes in the pericellular matrix of human articular cartilage

R E Wilusz et al. Osteoarthritis Cartilage. 2013 Dec.

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.

Keywords: Atomic force microscopy; Chondron; Proteoglycan; Scanning probe microscopy; Type VI collagen.

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Conflict of interest statement

CONFLICT OF INTEREST

None to declare.

Figures

Figure 1
Figure 1
Human knee joints were classified as (A) macroscopically normal or (B, C) arthritic, based on the presence and extent of surface fibrillation, fissures, and/or focal defects on the medial (M) or lateral (L) condyle. Representative knee joints for each Collins grade are shown.
Figure 2
Figure 2
Safranin-O (red, proteoglycans) and fast green (collagens, blue) staining of cartilage sections from both condyles of (A, B) macroscopically normal and (C, D) OA knee joints. Surface irregularities and a loss of proteoglycan staining are present in OA cartilage sections from the medial condyle. The AFM testing region in the middle and upper deep zones (200 – 400 μm from the articular surface) is labeled in each image (yellow rectangle). Scale bar = 300 μm.
Figure 3
Figure 3
(A, B) Representative images of immunofluorescence labeling of type VI collagen in cartilage from (A) macroscopically normal and (B) OA knee joints. Scale bar = 100 μm (C, D) Immunofluorescence labeling revealed expanded regions that were positive for type VI collagen in the PCM of OA cartilage. Scale bar = 25 μm.
Figure 4
Figure 4
Elastic moduli of cartilage ECM and PCM from the (A) medial and (B) lateral condyles of macroscopically normal (grey) and OA (white) knee joints. Testing regions from the same joint are represented by the same symbol. a: p < 0.001 for normal ECM moduli as compared to OA ECM moduli on the medial condyle. b: p < 0.001 for ECM moduli as compared to their respective PCM moduli on the medial condyle. c: p = 0.036 for normal PCM moduli as compared to OA PCM moduli on the medial condyle. d: p < 0.001 for ECM moduli as compared to their respective PCM moduli on the lateral condyle. Moduli presented individually with means with 95% confidence interval represented by the black overlaid lines (N = 4 knees, n = 15 – 16 regions per classification).
Figure 5
Figure 5
Elastic mapping of PCM regions from the medial (A, B, C) and lateral condyles (D, E, F) of macroscopically normal and OA knee joints. (A, B) Representative contour maps of calculated elastic moduli for PCM scan regions of (A, D) normal and (B, E) OA cartilage from both condyles. Contour maps are presented on the same graded coloring scale and cell-sized voids are depicted in white. (C) Outward progression of elastic moduli from the PCM inner edge to the ECM of normal (grey) and OA (white) medial condyle cartilage. a: p < 0.01 for normal cartilage moduli within 1.5 μm of the PCM inner edge (p < 0.001 for 0.5 μm and 1.0 μm; p = 0.009 for 1.5 μm) as compared to normal moduli at a distance of 3.0 μm. b: p < 0.05 for OA cartilage moduli within 1.0 μm of the PCM inner edge (p = 0.047 for 0.5 μm; p = 0.016 for 1.0 μm) as compared to OA moduli at a distance of 3.0 μm. c: p < 0.05 for OA ECM moduli as compared to all distances in OA cartilage (p < 0.001 for 0.5 μm to 5.0 μm; p = 0.001 for 5.5 μm; p = 0.004 for 6.0 μm; p = 0.018 for 6.5 μm; p = 0.046 for 7.0 μm). #: Normal cartilage moduli were not significantly different from normal ECM values beginning 6.0 μm from the PCM inner edge (p = 0.065 for 6.0 μm; p = 0.191 for 6.5 μm; p = 0.478 for 7.0 μm). Moduli presented as means with 95% confidence interval (N = 4 knees, n = 15 – 16 regions per classification). (F) Outward progression of elastic moduli from the PCM inner edge to the ECM of normal (grey) and OA (white) lateral condyle cartilage. d: p < 0.05 for normal cartilage moduli within 1.5 μm of the PCM inner edge (p < 0.001 for 0.5 μm and 1.0 μm; p = 0.017 for 1.5 μm) as compared to normal moduli at a distance of 3.0 μm. e: p < 0.05 for normal ECM moduli as compared to all distances in normal cartilage (p < 0.001 for 0.5 μm to 5.0 μm; p = 0.002 for 5.5 μm; p = 0.006 for 6.0 μm; p = 0.017 for 6.5 μm; p = 0.043 for 7.0 μm). f: p < 0.05 for OA cartilage moduli within 1.5 μm of the PCM inner edge (p < 0.001 for 0.5 μm and 1.0 μm; p = 0.016 for 1.5 μm) as compared to OA moduli at a distance of 3.0 μm. g: p < 0.05 for OA ECM moduli as compared to all distances in OA cartilage (p < 0.001 for 0.5 μm to 5.5 μm; p = 0.004 for 6.0 μm; p = 0.017 for 6.5 μm; p = 0.049 for 7.0 μm). Moduli presented as means with 95% confidence interval (N = 4 knees, n = 15 – 16 regions per classification).
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