DIFFERENCES IN METABOLISM AND PROTECTIVE-RESPONSE OF ARTICULAR CARTILAGE DEPENDING ON DIFFERENT COMBINATIONS OF RUNNING INTENSITY, DURATION, AND FREQUENCY IN MICE

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Wakimoto Y1, Mizuno E1, Nomura M1,2, Suzuki R1, Inoue S1, Yakuwa T1, Li C1, Wakigawa T3, Tsubaki T3, Hatakeyama J3, Kinoshita S3, Moriyama H4
1Kobe University Graduate School of Health Sciences, Department of Rehabilitation Science, Kobe, Japan, 2Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan, 3Kobe University School of Medicine Faculty of Health Sciences, Physical Therapy Major, Kobe, Japan, 4Kobe University, Life and Medical Sciences Area, Health Sciences Discipline, Kobe, Japan

Background: Knee cartilage degeneration, such as osteoarthritis, affects on health and quality of life in the middle-aged and elderly people. Running is a general and effective exercise therapies to promote health. Mechanical stress generated by running is an important factor for regulating the cartilage metabolism in knee joint. While the appropriate stress benefits cartilage, the excessive stress has negative effects on cartilage and leads to the cartilage degeneration. Running protocol is mainly set by the intensity, duration, and frequency. The different combination of them alters the stress on cartilage, resulting in the different cartilage responses. However, the effects of different running protocol on cartilage response is still poorly understood.

Purpose: The purpose of this study was to revealthe differences in cartilage response depending on different combinations of the intensity, duration, and frequency in running exercise, and to provide the most appropriate running protocol to maintain the knee cartilage in better state.

Methods: Twenty-seven male C57BL/6J mice, 8 weeks of age, were randomly divided into control group (no exercise) and following 8 treadmill exercise groups:
1) high-intensity, long-duration, and high-frequency (HLH) group;
2) high-intensity, short-duration, and high-frequency (HSH) group;
3) high-intensity, long-duration, and low-frequency (HLL) group;
4) high-intensity, short-duration and low-frequency (HSL) group;
5) low-intensity, long-duration, and high-frequency (LLH) group;
6) low-intensity, short-duration, and high-frequency (LSH) group;
7) low-intensity, long-duration, and low-frequency (LLL) group; and
8) low-intensity, short-duration, and low-frequency (LSL) group.
The exercise intensity was set 18 m/min (high-intensity) and 8 m/min (low-intensity). The exercise duration was set 60 min/day (long-duration) and 15 min/day (short-duration). The exercise frequency was set everyday (high-frequency) and once in 3 days (low-frequency). After each exercise for 4 weeks, we evaluated cartilage thickness, cartilage matrix metabolism, and chondroprotective protein (lubricin) in the articular cartilage of tibia by histological and immunohistochemical analyses. In statistical analysis, one-way ANOVA with Tukey's post hoc test was used to compare each group. The significance level was set at 5%.

Results: In the HLH group, the percentage of lubricin-positive chondrocyte and MMP13-positive chondrocytes were significantly increased, and cartilage thickness was decreased. In the LSH group, although the percentage of lubricin-positive chondrocyte was not significantly different from the control group, the percentage of ADAMTS5-positive chondrocyte was significantly lower and the percentage of aggrecan-positive area and the thickness of cartilage were significantly larger than that in the HLH group.

Conclusion(s): This study indicates the high-intensity, long-duration, and high-frequency running exercise may enhance both the catabolic and chondroprotective responsesin cartilage, leading to decreases in cartilage thickness. Conversely, low-intensity, short-duration, and high-frequency running exercise may accelerate the anabolic response of cartilage, leading to increases in cartilage thickness.

Implications: Based on our findings, to maintain the knee cartilage in better state, the acceleration of anabolic response may be more important than increased expression of chondroprotective protein. From this point of view, the low-intensity, short-duration, and high-frequency running may be the most recommended exercise protocol.

Keywords: Articular cartilage response, Metabolism and protective response, Recommended running protocol

Funding acknowledgements: This study was supported in part by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 25702032.

Topic: Musculoskeletal: lower limb; Musculoskeletal; Sport & sports injuries

Ethics approval required: Yes
Institution: Kobe University
Ethics committee: The Institutional Animal Care and Use Committee
Ethics number: P140603


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