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Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model
  1. Fumiko Yano1,
  2. Shinsuke Ohba2,
  3. Yoko Hosaka3,
  4. Taku Saito3,
  5. Ung-il Chung1,2
  1. 1Center for Disease Biology and Integrative Medicine, University of Tokyo, Tokyo, Japan
  2. 2Department of Bioengineering, The University of Tokyo, Tokyo, Japan
  3. 3Sensory and Motor System Medicine, The University of Tokyo, Tokyo, Japan
  1. Correspondence to Dr Fumiko Yano, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; yanof-ora{at}h.u-tokyo.ac.jp

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We previously reported that a thienoindazole derivative TD-198946 (TD) induced chondrogenic differentiation in vitro without promoting hypertrophy, and prevented and repaired the degeneration of articular cartilage observed in a surgically induced mouse model of osteoarthritis (OA).1 In that study, the TD injections into mouse knee joints began on the day of the OA surgery (prevention model) or 4 weeks after the surgery (repair model), and continued periodically until 8 weeks after the surgery.1

Here we report the disease-modifying effects of TD injections on progressed OA in mice. We examined 4-week and 8-week injection protocols that began 8 weeks after the OA surgery (figure 1A). Eight mice in each group (n=8) were then subjected to histopathological assessments of knee joint OA. The severity of OA was quantified using the Osteoarthritis Research Society International histopathology scoring system (scale: 0–6)2 on histological sections stained with Safranin O/fast green. The OA surgery, preparation of TD, injection of TD into mouse knee joints and preparation of paraffin sections were performed as …

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