Spontaneous osteoarthritis in Str/ort mice is unlikely due to greater vulnerability to mechanical trauma B. Poulet, T.A.T. Westerhof, R.W. Hamilton,

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Spontaneous osteoarthritis in Str/ort mice is unlikely due to greater vulnerability to mechanical trauma B. Poulet, T.A.T. Westerhof, R.W. Hamilton, S.J. Shefelbine, A.A. Pitsillides Osteoarthritis and Cartilage Volume 21, Issue 5, Pages 756-763 (May 2013) DOI: 10.1016/j.joca.2013.02.652 Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 FE geometry and mesh and displacement of the femur relative to the tibia during loading. (A) FE with the assigned boundary conditions, bone is in green and cartilage in blue. Arrows show the direction of the loads applied. (B) Segmented data from the microCT scans showing the changes in positions of the femur relative to the tibia before (green) and during loading (red). This was used to determine the direction of the loading for the FE modeling described in A. (C and D) Contact pressure on the femoral (C) and tibial (D) condyles. (E and F) Contact shear on the femoral (E) and tibial (F) condyles. (Femurs are viewed from the posterior side and tibia from the top.) Osteoarthritis and Cartilage 2013 21, 756-763DOI: (10.1016/j.joca.2013.02.652) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Loading does not induce AC lesions in the LF of 8-week-old Str/ort mice. (A) Mean and maximum AC lesion severity scores are not increased between control (open) and loaded (hashed) Str/ort mouse knee joints (n = 8). (B) AC was thicker in all compartments of the knee joint in 8-week-old Str/ort mice (white) compared to CBA mice (grey). Data shown as mean with 95% CI, statistical significance is marked P < 0.001 between CBA and Str/ort mice. Osteoarthritis and Cartilage 2013 21, 756-763DOI: (10.1016/j.joca.2013.02.652) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Contact area during loading. (A) Contact pressures on the femoral lateral condyle increase, but remain in the same position during loading. Contour lines indicate relative magnitude of pressure for the contact area, which increases during loading. Black lines in the far right are sums of the contact area for the entire loading cycle and indicate the location of minimum (outer), mean, and maximum (inner) contact areas. This provides an indication of how the contact area moves during loading. (B) In contrast, the contact pressure on the lateral tibia moves during loading, resulting in increased contact area during loading. (C–H) Contour plots from the three different femoral cartilage thicknesses (20, 40 and 80 μm) on the posterior condyles of the femur, indicating highest contact pressure and shear in the thinnest cartilage. (Note: total displacement is similar in each of these three models, but different from the loading shown in [Fig. 1(C–F)] to accommodate the different thickness.) Osteoarthritis and Cartilage 2013 21, 756-763DOI: (10.1016/j.joca.2013.02.652) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Loading increases AC degeneration in OA-prone medial tibia of 8-week-old Str/ort mice. (A) Mechanical loading increased AC lesion severity mean and maximum scores in the medial tibia. Data shown as mean with 95% CI. (B–E) Safranin O staining was decreased around AC lesions in the MT of right loaded (C) vs left non-loaded (B) Str/ort mice (proteoglycan (PG) loss; B and C), and collagen degradation products, detected by immunohistochemistry (C1, 2C; D and E), were strongly labelled in the extracellular matrix (ECM) surrounding AC lesions in MT of right loaded (E) compared to left non-loaded (D) joints of Str/ort mice. (F) Section incubated with rabbit IgG lacking primary antibody (control for E). Osteoarthritis and Cartilage 2013 21, 756-763DOI: (10.1016/j.joca.2013.02.652) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions