Mechanism of the protective effect of high molecular weight hyaluronic acid against cartilage degeneration

  • Harada Mari
    Department of Pathology, Iwate Medical University, School of Medicine
  • Uzuki Miwa
    Department of Pathology, Iwate Medical University, School of Medicine Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University
  • Naoki Ishiguro
    Department of Orthopedics, Nagoya University, Graduate School of Medicine
  • Iwadate Katsuji
    New Drug Research Center. Inc
  • Sawai Takashi
    Department of Pathology, Iwate Medical University, School of Medicine Sendai Open Hospital, Sendai city Medical care Center Department of Pathology, Tohoku University, Graduate School of Medicine

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Other Title
  • 高分子ヒアルロン酸(HA)による軟骨保護作用のメカニズムの解明

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Purpose: The therapeutic effect of hyaluronic acid (HA) on osteoarthritis (OA) was assessed in Kb1 rabbits by histopathological examination.<br> Materials: An OA model was prepared in rabbits according to Ishiguro’s method. Then an HA preparation (SUVENYL HA [ MW 2.7 million Da] or Synvisc HA [mixture of cross-linked HA prepared from rooster’ combs]) or saline was repeatedly injected into the left knee joint of the each rabbit. Knee joint tissues were fixed in 10% formalin and paraffin embedded specimens were routinely processed for histological examination.<br> Methods: The therapeutic effect of HA on joint cartilage was assessed from the following three sets of parameters: (1) maintenance of proteoglycan, HA, or type II collagen; (2) degeneration of the extra cellular matrix and cartilage, assessed by observing aggrecan degradation products or apoptotic cells; and (3) remodeling evaluated by staining with Ki67 or detection of hyaluronan synthase (HAS) 2 or 3 mRNA.<br> Results: The histological grade of OA for the tibial compartment was 4.81 ± 0.25 in the saline group, and 4.69 ± 0.25 in the SVENYL HA-treated group, and 4.77 ± 0.26 in the Synvisc HA-treated group, while the grade for femoral compartment were 4.69 ± 0.25, 4.35 ± 0.43 and 4.38 ± 0.30, respectively. The residual levels of proteoglycan, type II collagen, and HA were increased in the femurs of the two HA- treated groups compared with the saline group. In addition, the positive ratio of apoptosis and aggrecan degradation products were significantly decreased in the HA-treaed groups compared with the saline group. Moreover, the number of Ki67 positive cells and the expression of HAS2 and HAS3 mRNAs were significantly greater in HA-treated groups than in the saline group. In the tibia, the trends of these parameters were similar to those for femur, but differences among the three groups were smaller.<br> Conclusions: Efficacy of HA was demonstrated by a reduction of parameters indicating cartilage damage, and an increase of parameters indicating a remodeling effect on cartilage.

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