HISTOPATHOLOGICAL CHANGES IN ARTICULAR CARTILAGE AND LOCOMOTOR ACTIVITY OF EXPERIMENTAL OSTEOARTHRITIS MODEL IN MICE

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Kojima S1, Watanabe M2, Asada K3, Hoso M4
1Kinjo University, Course of Rehabilitation, Graduate School of Rehabilitation, Hakusan, Japan, 2Nagoya Gakuin University, Department of Physical Therapy, Faculty of Rehabilitation Science, Seto, Japan, 3Suzuka University of Medical Science, Department of Physiotherapy, Faculty of Health Science, Suzuka, Japan, 4Kanazawa University, Division of Health Sciences, Graduate School of Medical Science, Kanazawa, Japan

Background: Excessive mechanical stress on joints is one of the factors that cause osteoarthritis (OA). However, adequate mechanical stress is understood to be beneficial for chondral repair. Some OA models have been created in previous studies on animals, and various reports have elucidated the pathology describe chondral repair (Lampropoulou, et. al; 2014). However, the relationship between amount of exercise and changes in articular cartilage caused by OA remains unknown, as there are no previous reports that have investigated this to date.

Purpose: This study aimed to compare changes in articular cartilage and locomotor activity for experimental osteoarthritis model at three levels of progression in mice.

Methods: Twenty-four 6-month-old male ICR mice were used. Six mice were randomly assigned to each of the four groups that underwent the following procedures: medial collateral ligament transection (MCLT group), destabilization of the medial meniscus by transection of the medial meniscotibial ligament (DMM group), transection of the medial meniscotibial ligament and anterior cruciate ligament transection (DMM+ACLT group) and the control group. OA was surgically induced bilaterally on the knees of the destabilization model by making an incision to the skin on the medial side of the knee under anesthesia and transecting the MCL only (MCL group), transecting the medial meniscotibial ligament only (DMM group) and transecting the medial meniscotibial and anterior cruciate ligaments (DMM+ACLT group). Mice were kept in a cage for 8 postoperative weeks and amount of exercise was measured by an infrared locomotor activity measurement device. After completion of the experimental period, the knee tissues were subjected to paraffin embedding according to the routine procedure for tissue specimen preparation. The sections were stained with HE or safranin O/fast green, and subjected to optical microscopy. The degree of cartilage degeneration was scored and a multiple comparison test was performed.

Results: Histological findings included prolapsed medial meniscus, irregular surface layer of cartilage, fibrillation and eburnation in the DMM and DMM+ACLT groups. These findings were more severe in the DMM+ACLT group. Findings of the MCL group were similar to those of the control group, and there was no significant difference in chondral degeneration score. Locomotor activity declined significantly on the first postoperative week in the MCL, DMM and DMM+ACLT groups compared to the control group. Amount of exercise subsequently increased gradually until their levels improved to levels equal to the control group on the third postoperative week and later.

Conclusion(s): In the mouse, changes in locomotor activity were not found regardless of the degree of damage of the articular cartilage induced by OA.

Implications: The decline in activity in person with OA causes decreased muscular strength, which further promotes the progression of OA (Mahmoudian, et al; 2018). Adequate exercise and mechanical stress is important for maintenance and repair of OA cartilage, but the specific amount and method are unknown. This study was important as basic research to elucidate the relationship between OA progression and amount of exercise.

Keywords: Osteoarthritis, motor activity, mice

Funding acknowledgements: This work supported by JSPS KAKENHI Grant Number 16K01526 and Kinjo University Special Research Grant 2017.

Topic: Musculoskeletal; Orthopaedics

Ethics approval required: Yes
Institution: Kinjo University
Ethics committee: Animal Care and Use Committee
Ethics number: 8


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