EFFECT OF LOW-INTENSITY PULSED ULTRASOUND ON PREVENTION OF JOINT CARTILAGE IN A SURGICALLY INDUCED OSTEOARTHRITIC RAT MODEL

Watanabe M1, Kojima S2, Asada K3, Hoso M4
1Nagoya Gakuin University, Department of Physical Therapy, Faculty of Rehabilitation Science, Seto, Japan, 2Graduate School of Rehabilitation, Kinjo University, Course of Rehabilitation, Hakusan, Japan, 3Suzuka University of Medical Science, Department of Physiotherapy, Faculty of Health Science, Suzuka, Japan, 4Graduate School of Medical Science, Kanazawa University, Division of Health Sciences, Kanazawa, Japan

Background: Recently, the indications of low-intensity pulsed ultrasound (LIPUS) have been expanded to include treatment of cartilage damage, not limited to treatment of bone fractures. Applying LIPUS to the site of cartilage damage has been reported to reduce matrix metalloproteinases (MMPs), while increasing tissue inhibitor of metalloprotease (TIMP) as well as type II collagen and chondroitin sulfate (Rothenberg et al.; 2017). While it is best to intervene as early as possible for osteoarthritis cases due to the poor regenerative capacities of cartilage tissue, there have been few studies on the preventive effects of LIPUS in mild cartilage damage models, and these effects remain unknown.

Purpose: To clarify the histologically effects of LIPUS in preventing the progression of cartilage damage using a rat model of slowly progressive post-traumatic osteoarthritis (OA).

Methods: Twelve 12-week-old Wistar male rats were used in this study. The bilateral medial meniscotibial ligaments were surgically removed to gradually cause OA (Glasson et al.; 2005). Rats were kept under normal conditions for a week after surgery and were randomly divided into the treatment group and the control group (n=6 per group). LIPUS were administered to the rats in the treatment group for 15 minutes per day for 3 weeks at frequency of 3 MHz with intensity of 30 mW/cm2 SATA and duty cycle of 20%, while sham treatment was administered in the control group under the same conditions. After the treatment period ended, all rats were euthanized and both sides of the knee joints were removed. Specimens were prepared for histological analysis on the frontal planes of the knee joints. Hematoxylin and eosin staining as well as safranin O and fast green staining were performed, and the sections were observed under an optical microscope. Joint cartilage findings in both groups were scored and compared using t-test.

Results: Inward displacement of the meniscus was confirmed in both groups, and decreased matrix staining, irregularity of the cartilage surface layer, and fibrillation were observed localized around the tip of the meniscus toward the center of the joint. No marked differences were noted in the level of cartilage damage between the two groups, and no significant score differences were detected.

Conclusion(s): LIPUS was unable to reduce progression of cartilage damage in our study. Further verification is required.

Implications: OA affects a very large number of patients worldwide. While LIPUS is also starting to be indicated for human OA cases (Zhou et al.; 2018), its effects are limited. In this context, clarifying the indications of LIPUS in basic research could greatly contribute to the future development of electrophysical agents.

Keywords: osteoarthritis, LIPUS, rat

Funding acknowledgements: This work was supported by JSPS KAKENHI Grant Number 16K01526 and a research grant in 2018 from Nagoya Gakuin University.

Topic: Musculoskeletal; Electrophysical & isothermal agents

Ethics approval required: Yes
Institution: Nagyoa Gakuin University
Ethics committee: Animal Experiments Committee of Nagyoa Gakuin University
Ethics number: approval number: 2013-001


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