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

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.

Minor Influence of Lifelong Voluntary Exercise on Composition, Structure, and Incidence of Osteoarthritis in Tibial Articular Cartilage of Mice Compared with Major Effects Caused by Growth, Maturation, and Aging

“…Thus, the energy expenditure of lid climbing can be almost comparable to the activity of running, even though the mode or pattern of exercise is different. However, the body weights of the runner mice have in separate experiments consistently been 2-16% lower, that is, significantly lower than the weight of the sedentary mice, speaking in favor of a true exercise effect of running wheel exercise [40,41,[48][49][50]. Therefore, it is reasonable to assume that running wheel exercise increases the amount of physical exercise compared with mice without running wheel exercise.…”

Does loading influence the severity of cartilage degeneration in the canine Groove‐model of OA?

“…[9][10][11][12] However, evaluation of the actual loading and mobility of the animals demonstrated a major drawback in the study setup. Although initially it was intended to create two groups of animals, one with significant loading of the surgically affected joint and one with minimal loading of the affected joint, this was not unambiguously achieved.…”

“…10 In transgenic Del1 mice, running activity causes an increase in incidence and severity of degenerative changes in the articular cartilage of knee joints within 15 months. 11 Forced mobilization of rats after ACLT and partial medial menisectomy leads to an increase in OA compared to normal mobilization, again indicating that loading is important in the development of OA. 12 More importantly, also in human OA, there is an increasing body of literature suggesting that the mechanical environment of the knee during ambulation has a profound influence on the severity, progression, and treatment outcome for osteoarthritis of the knee.…”

MR-Based In Vivo Analysis of Joint Biomechanics and its Relevance in the Pathogenesis of Osteoarthritis

“…Data of the relevance of these factors is usually based on animal models [210,211], in vitro simulations [212] or epidemiological analysis [11-13, 21, 22].…”