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

Katri, A.; Dąbrowska, A.; Löfvall, H. LU ; Karsdal, M. A.; Andreassen, K. V.; Thudium, C. S. LU and Henriksen, K. (2019) In Osteoarthritis and Cartilage
Abstract

Objectives: Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the effect of KBP in a rat model of osteoarthritis. Methods: Medial meniscectomy (MNX) was performed in 39 rats, while 10 underwent sham surgery. Rats were treated with KBP and/or naproxen. Nociception was assessed by mechanical and cold allodynia, weight bearing asymmetry, and burrowing behavior. Blood samples were collected for biomarker measurements,... (More)

Objectives: Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the effect of KBP in a rat model of osteoarthritis. Methods: Medial meniscectomy (MNX) was performed in 39 rats, while 10 underwent sham surgery. Rats were treated with KBP and/or naproxen. Nociception was assessed by mechanical and cold allodynia, weight bearing asymmetry, and burrowing behavior. Blood samples were collected for biomarker measurements, and knees for histology. Cartilage histopathology was evaluated according to the advanced Osteoarthritis Research International (OARSI) score and KBPs in vitro antiresorptive effects were assessed using human osteoclasts cultured on bone. Results: The MNX animals displayed an increased nociceptive behavior. Treatment with KBP attenuated the MNX-induced osteoarthritis-associated joint pain. The cartilage histopathology was significantly lower in rats treated with KBP than in MNX animals. Bone and cartilage degradation, assessed by CTX-I and CTX-II plasma levels, were decreased in all KBP-treated groups and KBP potently inhibited bone resorption in vitro. Conclusions: Our study demonstrates the effectiveness of KBP in ameliorating osteoarthritis-associated joint pain and in protecting the articular cartilage, suggesting KBP as a potential drug candidate for osteoarthritis.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Animal models, Bone, Dual amylin-calcitonin receptor agonist, Osteoarthritis, Pain, Treatment
in
Osteoarthritis and Cartilage
publisher
Elsevier
external identifiers
  • scopus:85067436194
ISSN
1063-4584
DOI
10.1016/j.joca.2019.05.016
language
English
LU publication?
yes
id
392b8656-a8c8-4708-a654-b25048e8c9c6
date added to LUP
2019-07-05 13:07:00
date last changed
2019-07-30 05:06:08
@article{392b8656-a8c8-4708-a654-b25048e8c9c6,
  abstract     = {<p>Objectives: Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the effect of KBP in a rat model of osteoarthritis. Methods: Medial meniscectomy (MNX) was performed in 39 rats, while 10 underwent sham surgery. Rats were treated with KBP and/or naproxen. Nociception was assessed by mechanical and cold allodynia, weight bearing asymmetry, and burrowing behavior. Blood samples were collected for biomarker measurements, and knees for histology. Cartilage histopathology was evaluated according to the advanced Osteoarthritis Research International (OARSI) score and KBPs in vitro antiresorptive effects were assessed using human osteoclasts cultured on bone. Results: The MNX animals displayed an increased nociceptive behavior. Treatment with KBP attenuated the MNX-induced osteoarthritis-associated joint pain. The cartilage histopathology was significantly lower in rats treated with KBP than in MNX animals. Bone and cartilage degradation, assessed by CTX-I and CTX-II plasma levels, were decreased in all KBP-treated groups and KBP potently inhibited bone resorption in vitro. Conclusions: Our study demonstrates the effectiveness of KBP in ameliorating osteoarthritis-associated joint pain and in protecting the articular cartilage, suggesting KBP as a potential drug candidate for osteoarthritis.</p>},
  author       = {Katri, A. and Dąbrowska, A. and Löfvall, H. and Karsdal, M. A. and Andreassen, K. V. and Thudium, C. S. and Henriksen, K.},
  issn         = {1063-4584},
  keyword      = {Animal models,Bone,Dual amylin-calcitonin receptor agonist,Osteoarthritis,Pain,Treatment},
  language     = {eng},
  month        = {06},
  publisher    = {Elsevier},
  series       = {Osteoarthritis and Cartilage},
  title        = {A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model},
  url          = {http://dx.doi.org/10.1016/j.joca.2019.05.016},
  year         = {2019},
}