A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model A. Katri, A. Dąbrowska,

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General Information Osteoarthritis and Cartilage

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A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model A. Katri, A. Dąbrowska, H. Löfvall, M.A. Karsdal, K.V. Andreassen, C.S. Thudium, K. Henriksen Osteoarthritis and Cartilage Volume 27, Issue 9, Pages 1339-1346 (September 2019) DOI: 10.1016/j.joca.2019.05.016 Copyright © 2019 The Author(s) Terms and Conditions

Fig. 1 Body weight monitoring. Change in body weight presented as % of initial body weight. Error bars indicate the SEM, n = 10/group except n = 9 in MNX group. Statistical significance compared to the MNX is indicated by *P < 0.05, **P < 0.01, and ***P < 0.001. Osteoarthritis and Cartilage 2019 27, 1339-1346DOI: (10.1016/j.joca.2019.05.016) Copyright © 2019 The Author(s) Terms and Conditions

Fig. 2 Effect of KBP on cartilage pathology 8 weeks after surgery. Representative micrographs of the medial tibia plateau stained with SafO + Fast green staining (A) to assess cartilage damage according to the Osteoarthritis Research International (OARSI) advanced grading methology (B). Scale bars in A indicate 200 μm. Statistical significance compared to the MNX in B is indicated by *P < 0.05, **P < 0.01, and ***P < 0.001. n = 9 for the MNX, sham and MNX + KBP + Napr, and n = 10 for the MNX + KBP and MNX + Napr groups. Osteoarthritis and Cartilage 2019 27, 1339-1346DOI: (10.1016/j.joca.2019.05.016) Copyright © 2019 The Author(s) Terms and Conditions

Fig. 3 Effect of KBP on pain behavior in the MNX model. Pain-like behaviors were assessed using paw withdrawal thresholds (A), cold hypersensitivity (B), burrowing behavior (C), and weight bearing asymmetry (D). Data in A are presented as the percent change from baseline and data in B are presented as the mean change from baseline. Error bars indicate the SEM, n = 10/group except n = 9 in MNX group. Statistical significance compared to the MNX is indicated by *P < 0.05, **P < 0.01, and ***P < 0.001. Osteoarthritis and Cartilage 2019 27, 1339-1346DOI: (10.1016/j.joca.2019.05.016) Copyright © 2019 The Author(s) Terms and Conditions

Fig. 4 KBP inhibits bone resorption and cartilage degradation in vivo. Bone resorption and cartilage degradation was assessed by CTX-I (A) and CTX-II (B), respectively. For CTX-I; MNX n = 9; sham n = 10; CIA + KBP n = 10; CIA + Napr n = 10; MNX + KBP + Napr n = 9. For CTX-II; MNX n = 10; sham n = 10; CIA + KBP n = 9; CIA + Napr n = 10; MNX + KBP + Napr n = 9. Data are presented as the mean fraction of each rat's baseline measurement. Error bars indicate the SEM. Statistical significance compared to the MNX is indicated by *P < 0.05, **P < 0.01, and ***P < 0.001. Osteoarthritis and Cartilage 2019 27, 1339-1346DOI: (10.1016/j.joca.2019.05.016) Copyright © 2019 The Author(s) Terms and Conditions

Fig. 5 KBP inhibits osteoclastic bone resorption in vitro inhibition. Resorption of type I collagen was assessed by measuring CTX-I. Data are presented as the mean ± SEM. Statistical significance between treated conditions and the vehicle is indicated by *P < 0.05, **P < 0.01, and ***P < 0.001. Osteoarthritis and Cartilage 2019 27, 1339-1346DOI: (10.1016/j.joca.2019.05.016) Copyright © 2019 The Author(s) Terms and Conditions