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Therapeutic effects of high molecular weight hyaluronan injections for tendinopathy in a rat model

  • Original Article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

Tendinopathy is the most common tendon disorder. The etiology is still uncertain, and the disorder poses many therapeutic problems. In a few clinical studies, analgesic effects of high molecular weight hyaluronan (HMW HA) injections were observed, but the underlying mechanisms were not elucidated. In the present study, we analyzed the therapeutic effects of hyaluronan injections for tendinopathy in an animal model.

Methods

We made the tendinopathy rat model using a rodent treadmill machine. Rats with tendinopathy were injected with HMW HA (HA group), normal saline (NS group), or nothing (control group) into the space between the patellar tendon and the fat pad bilaterally, or were injected with HMW HA into the right knees and with saline to the left knees (HA/NS group), 5 times every 4 days. To assess the pain-relieving effect of HA, the spontaneous locomotor activities at night (12 h) and weight bearing of hind paws were measured every day. Histological sections of the patellar tendon stained with hematoxylin–eosin or prepared by TdT-mediated dUTP nick end labeling were microscopically analyzed.

Results

The number of spontaneous locomotor activities in the HA group was significantly larger than those in NS or control groups, and in the HA group they recovered up to a healthy level. The percent weight distribution of the right hind paws was significantly increased along with the number of injections. On histologic examinations, the numbers of microtears, laminations, or apoptotic cells in the patellar tendons in the HA group were significantly lower than those in the NS or the control groups.

Conclusions

The injections of HMW HA were effective for pain relief and for partial restoration of the patellar tendon in our tendinopathy rat model, and thus may become an effective therapeutic modality for the disease.

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Abbreviations

HMW HA:

High molecular weight hyaluronan

NS:

Normal saline

EDTA:

Ethylenediamine tetra-acetic acid

H&E:

Hematoxylin–eosin

TUNEL:

TdT-mediated dUTP nick end labeling

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Acknowledgments

We are grateful to all members of the Department of Orthopaedic Surgery of the Jikei University School of Medicine for the partial support of the present study, and appreciate Chugai Pharmaceutical Co., Ltd. for their financial support.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan

    Mamoru Yoshida, Hiroki Funasaki, Makoto Kubota & Keishi Marumo

Authors
  1. Mamoru Yoshida
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  2. Hiroki Funasaki
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  3. Makoto Kubota
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  4. Keishi Marumo
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Correspondence to Mamoru Yoshida.

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Yoshida, M., Funasaki, H., Kubota, M. et al. Therapeutic effects of high molecular weight hyaluronan injections for tendinopathy in a rat model. J Orthop Sci 20, 186–195 (2015). https://doi.org/10.1007/s00776-014-0650-z

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  • DOI: https://doi.org/10.1007/s00776-014-0650-z

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