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. 2002 Sep;61(9):810–817. doi: 10.1136/ard.61.9.810

Lifelong voluntary joint loading increases osteoarthritis in mice housing a deletion mutation in type II procollagen gene, and slightly also in non-transgenic mice

T Lapvetelainen 1, M Hyttinen 1, A Saamanen 1, T Langsjo 1, J Sahlman 1, S Felszeghy 1, E Vuorio 1, H Helminen 1
PMCID: PMC1754230  PMID: 12176806

Abstract

Objectives: To investigate the effects of voluntary running on the incidence and severity of osteoarthritis (OA) and associated changes in cartilage matrix and subchondral bone in a transgenic Del1 mouse model for OA.

Methods: Del1 mice and their non-transgenic littermate controls were housed from the age of 5–6 weeks to 15 months in individual cages with running wheels. The running activity of each mouse was monitored for the entire 12 month period. Additional Del1 and control mice were housed in individual cages without running wheels. At the end of the experiment the severity of OA was evaluated by light microscopy, and the articular cartilage matrix changes by digital densitometry and quantitative polarised light microscopy.

Results: Lifelong voluntary running increased the incidence and severity of OA significantly in Del1 mice (transgenic runners), and slightly also in non-transgenic runners. Severe OA changes increased from 39% in transgenic non-runners to 90% in transgenic runners (p=0.006) in lateral tibial condyles, and from 24% to 80% (p=0.013) in lateral femoral condyles, respectively. The proteoglycan content of articular cartilage was reduced in transgenic runners in comparison with transgenic non-runners (p=0.0167), but a similar effect was not seen in non-transgenic runners compared with non-transgenic non-runners. No attributable differences were seen in the collagen network of articular cartilage or in the subchondral bone between any of the groups.

Conclusion: The Del1 mutation has earlier been shown to disturb the assembly of the cartilage collagen network and thereby increase the incidence and severity of OA with age. In this study, voluntary running was shown to increase further cartilage damage in the lateral compartments of the knee. This suggests that articular cartilage in Del1 mice is less resistant to physical loading than in control mice. Despite severe OA lesions in the knee joint at the age of 15 months, Del1 mice continued to run voluntarily 2–3 km every night.

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Figure 1 .

Figure 1

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Scoring of OA changes from the frontal tibiofemoral joint sections of the lateral joint compartment. In each figure the arrow points to the grade in question. (A) Grade 1 OA, superficial fibrillation, cell loss from the superficial zone, and striation of the cartilage. (B) Grade 2 OA, deeper defects extending into the uncalcified cartilage. (C) Grade 3 OA, defects extending into the calcified cartilage. (D) Grade 4 OA, lesions extending in the subchondral bone which exhibits sclerosis. (E) Synovial and joint capsule reaction (line with two arrowheads) and grade 3 OA. Asterisk indicates the presence of calcified, bone-like tissue. (F) Grade 4 OA and hypertrophied synovium and joint capsule (lines with two arrowheads). Scale bar = 100 µm. Safranin O staining.

Figure 2 .

Figure 2

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Weight development of the mice (mean (SD)). Mann-Whitney's U test.

Figure 3 .

Figure 3

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Daily running distances of the mice (mean (SD)).

Figure 4 .

Figure 4

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Average running speed of the mice (mean (SD)).

Figure 5 .

Figure 5

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Osteoarthritic changes in the knee joints of mice at the age of 15 months. Mann-Whitney's U test.

Figure 6 .

Figure 6

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Articular cartilage thickness (mean (SEM)) in medial tibial and femoral condyles at the age of 15 months. NS, non significant, Mann-Whitney's U test.

Figure 7 .

Figure 7

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Safranin O stain absorbances in the superficial, intermediate, and deep zones of medial tibial (A) and femoral (B) cartilage condyles. "Total" indicates the cumulative absorbance in all zones. The number of mice analysed in each group and each zone is given as a number in the bars. Absorbance is given in AIOD (SEM). Mann-Whitney's U test.

Figure 8 .

Figure 8

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Radiographs of the knee joints of non-transgenic (non) and transgenic (tg) Del1 mouse non-runners at the age of 6 and 15 months. Lateral compartments at the left side and medial compartments at the right side. Note the varus deformity and prominent subchondral sclerosis of the knee joint of the 15 month-old transgenic mouse.

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