Lifelong moderate running training increases the incidence and severity of osteoarthritis in the knee joint of C57BL mice

Lapveteläinen, Tuomo; Nevalainen, Timo; Parkkinen, Jyrki; Arokoski, Jari; Király, Kari; Hyttinen, Marko; Halonen, Paavo; Helminen, Heikki J.

doi:10.1002/ar.1092420204

Cited by 59 publications

(52 citation statements)

References 42 publications

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“…Rats who ran on a treadmill between the ages of 6 and 24 months showed more severe OA in the knee joints than did the control animals [62]. Lifelong moderate running (1 km/day) on a treadmill between 2 and 18 months of age increased the incidence and severity of OA in the knee joints of C57BL mice [63]. However, lifelong moderate running of beagle dogs showed no evidence of knee articular cartilage injury after 4 km/ day exercise on the treadmill, 5 days/weeks, for a total of 550 weeks [64].…”

Section: Increased Joint Loading and Weight-bearingmentioning

confidence: 91%

Regular joint loading in youth assists in the establishment and strengthening of the collagen network of articular cartilage and contributes to the prevention of osteoarthrosis later in life: a hypothesis

et al. 2000

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importance of regular joint loading in young age for the development of a well-organized and strong articular cartilage collagen network, which contributes to the prevention of OA later in life. The load-bearing properties of articular cartilage as well as the main features of the metabolism and turnover of proteoglycans (PGs) and collagen are briefly reviewed, especially in relation to joint loading. Prevention of OAThe knowledge of the pathogenesis of OA and its risk factors is today supplemented at an increasing pace, which makes the prospects for prevention of the disease more and more realistic [2][3][4][5][6][7][8]. OA is a disease with a multifactorial etiology. It affects not only the articular cartilage but the whole synovial joint organ. This implies that in addition to articular cartilage, the properties of the subchondral bone and ligaments, the weight-bearing conditions including the biomechanical alignment of the joint, the weakness of the shockabsorbing and weight-bearing muscles, and the integrity and proper function of the neuromuscular system must be taken into regard [9]. Even though the OA process in the joint structures is accomplished by biochemical signals, i.e., cytokines, growth factors, proteins and enzymes, the disease appears to be primarily driven by the local mechanical factors in the joint. Thus, the mechanical etiology of OA deserves ongoing close scrutiny [9].The primary prevention of OA emphasizes hindering the disease from affecting healthy persons [2,5]. Large epidemiological studies on OA have pointed out several risk factors that can be influenced by adjusting our lifestyles. For example, obese persons are instructed to reduce body weight and to carry out exercises to strengthen their lower limb muscles to reduce stress at

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Section: Increased Joint Loading and Weight-bearingmentioning

confidence: 91%

Regular joint loading in youth assists in the establishment and strengthening of the collagen network of articular cartilage and contributes to the prevention of osteoarthrosis later in life: a hypothesis

et al. 2000

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“…Similar downhill running regimens have been used in other studies of exercise effects in rats [8]. The running exercise was used primarily to standardize the minimal amount of exercise all rats were doing but also because we assumed joint loading might need to be greater than that of cage activity for the development of osteoarthritis [12,16,28]. Rats were housed in pairs and were monitored daily.…”

Section: Methodsmentioning

confidence: 99%

Selective joint denervation promotes knee osteoarthritis in the aging rat

Salo

Hogervorst

Seerattan

et al. 2002

Journal Orthopaedic Research

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Osteoarthritis is the most common joint disorder with aging, but its cause is unknown. Mice lose joint afferents with aging, and this loss precedes development of osteoarthritis. We hypothesized a loss of joint afferents is involved in the pathogenesis of osteoarthritis.To test this hypothesis, we denervated knee joints of 16 rats at age 2 months, by intra-articular injection o f an immunotoxin. The imrnunotoxin killed neurons after retrograde axonal transport to the cell body. At 16 or 24 months follow-up, each joint was histologically assessed and assigned an osteoarthritis score.At follow-up, the number of joint afferents had spontaneously decreased by 42% in control knees and 69%~ in denervated knees. We found that control knees developed osteoarthritic changes with aging. However, denervated knees had far more severe changes, as evidenced by a 54% higher average osteoarthritis score than control knees ( P = 0.0016, both groups 16 knees).These results suggest a loss of afferents predisposes a joint to osteoarthritis. We propose the spontaneous loss o f neurons with aging may be a normal developmental process. To explain the mechanism causing osteoarthritis, we suggest denervation permits aberrant joint loading, either by disturbing neuromuscular joint control, or by inducing joint laxity after neurogenic loss of tissue homeostasis.

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“…More specifically, in OA, the PGs of the superficial zone experience loss and the collagen fibril network in the surface-most cartilage becomes progressively disorganized [14][15][16][17]. Earlier findings have indicated that exercise may protect from OA, make the joint more prone to OA, or have no effect on the incidence of OA [8,[18][19][20][21][22]. Part of this controversy may be explained by variations in the amount of exercise and its duration, as well as the site investigated in the joint [16].…”

Section: Introductionmentioning

confidence: 99%

“…Hypothetically, the modification of cartilage composition due to exercise could protect the joint from OA during later periods of life [18,23]. Investigations of the simultaneous effects of aging and exercise on cartilage with different animal models have reported various types of outcomes [8,19,24]. Lifelong moderate and non-voluntary running exercise of C57BL mice between the ages of 2 and 18 months was shown to increase the incidence and severity of OA [19].…”

Section: Introductionmentioning

confidence: 99%

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

Närhi

Siitonen

Lehto

et al. 2011

Connective Tissue Research

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We investigated the effects of lifelong voluntary exercise on articular cartilage of mice. At the age of 4 weeks C57BL mice (n = 152) were divided into two groups, with one group serving as a sedentary control whereas the other was allowed free access to a running wheel from the age of 1 month onward. Mice were euthanized at four different time points (1, 2, 6, and 18 months of age). Articular cartilage samples were gathered from the load-bearing area of the tibial medial plateaus, and osteoarthritis was graded. Additionally, the proteoglycan content distribution was assessed using digital densitometry, collagen fibril orientation, and parallelism with polarized light microscopy, and collagen content using Fourier transform infrared imaging spectroscopy. The incidence of osteoarthritis increased with aging, but exercise had no effect on this trend. Furthermore, the structure and composition revealed significant growth, maturation, and age-dependent properties. Exercise exerted a minor effect on collagen fibril orientation in the superficial zone. Fibril orientation at 2 months of age was more perpendicular to surface (p < 0.05) in controls compared with runners, whereas the situation was reversed at the age of 18 months (p < 0.05). The collagen content of the superficial zone was higher (p < 0.01) at the age of 18 months in controls compared with runners but the proteoglycan content did not display any exercise-dependent changes. In conclusion, growth, maturation, and aging exerted a clear effect on integrity, structure, and composition of medial tibial plateau articular cartilage in mice, whereas lifelong voluntary exercise had only a minor effect on collagen architecture and content.

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Lifelong moderate running training increases the incidence and severity of osteoarthritis in the knee joint of C57BL mice

Abstract: According to our results, the moderate, long-lasting running exercise accelerates the development of osteoarthritis in the knee joints of C57BL mice.

Cited by 59 publications

References 42 publications

Regular joint loading in youth assists in the establishment and strengthening of the collagen network of articular cartilage and contributes to the prevention of osteoarthrosis later in life: a hypothesis

Regular joint loading in youth assists in the establishment and strengthening of the collagen network of articular cartilage and contributes to the prevention of osteoarthrosis later in life: a hypothesis

Selective joint denervation promotes knee osteoarthritis in the aging rat

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

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