Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10
Abstract Osteoarthritis (OA) is a major degenerative joint condition that causes articular cartilage destruction. It was recently found that enhancement of chondroclasts and suppression in Treg cell differentiation are involved in the pathogenesis of OA. Kartogenin (KGN) is a small drug-like molecul...
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2018
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oai:doaj.org-article:b046e22e941d47cb8e63906a174a3d142021-12-02T15:07:45ZKartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-1010.1038/s41598-018-32206-72045-2322https://doaj.org/article/b046e22e941d47cb8e63906a174a3d142018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32206-7https://doaj.org/toc/2045-2322Abstract Osteoarthritis (OA) is a major degenerative joint condition that causes articular cartilage destruction. It was recently found that enhancement of chondroclasts and suppression in Treg cell differentiation are involved in the pathogenesis of OA. Kartogenin (KGN) is a small drug-like molecule that induces chondrogenesis in mesenchymal stem cells (MSCs). This study aimed to identify whether KGN can enhance severe pain behavior and improve cartilage repair in OA rat model. Induction of OA model was loaded by IA-injection of MIA. In the OA rat model, treatment an intra-articular injection of KGN. Pain levels were evaluated by analyzing PWL and PWT response in animals. Histological analysis and micro-CT images of femurs were used to analyze cartilage destruction. Gene expression was measured by real-time PCR. Immunohistochemistry was analyzed to detect protein expression. KGN injection significantly decreased pain severity and joint destruction in the MIA-induced OA model. KGN also increased mRNA levels of the anti-inflammatory cytokine IL-10 in OA patients’ chondrocytes stimulated by IL-1β. Decreased chondroclast expression, and increased Treg cell expression. KGN revealed therapeutic activity with the potential to reduce pain and improve cartilage destruction. Thus, KGN could be a therapeutic molecule for OA that inhibits cartilage damage.Ji Ye KwonSeung Hoon LeeHyun-Sik NaKyungAh JungJeongWon ChoiKeun Hyung ChoChang-Yong LeeSeok Jung KimSung-Hwan ParkDong-Yun ShinMi-La ChoNature PortfolioarticleKartogenin (KGN)ChondroclastsTreg Cell DifferentiationTreg CellsCartilage DestructionMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) |
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Kartogenin (KGN) Chondroclasts Treg Cell Differentiation Treg Cells Cartilage Destruction Medicine R Science Q |
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Kartogenin (KGN) Chondroclasts Treg Cell Differentiation Treg Cells Cartilage Destruction Medicine R Science Q Ji Ye Kwon Seung Hoon Lee Hyun-Sik Na KyungAh Jung JeongWon Choi Keun Hyung Cho Chang-Yong Lee Seok Jung Kim Sung-Hwan Park Dong-Yun Shin Mi-La Cho Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10 |
description |
Abstract Osteoarthritis (OA) is a major degenerative joint condition that causes articular cartilage destruction. It was recently found that enhancement of chondroclasts and suppression in Treg cell differentiation are involved in the pathogenesis of OA. Kartogenin (KGN) is a small drug-like molecule that induces chondrogenesis in mesenchymal stem cells (MSCs). This study aimed to identify whether KGN can enhance severe pain behavior and improve cartilage repair in OA rat model. Induction of OA model was loaded by IA-injection of MIA. In the OA rat model, treatment an intra-articular injection of KGN. Pain levels were evaluated by analyzing PWL and PWT response in animals. Histological analysis and micro-CT images of femurs were used to analyze cartilage destruction. Gene expression was measured by real-time PCR. Immunohistochemistry was analyzed to detect protein expression. KGN injection significantly decreased pain severity and joint destruction in the MIA-induced OA model. KGN also increased mRNA levels of the anti-inflammatory cytokine IL-10 in OA patients’ chondrocytes stimulated by IL-1β. Decreased chondroclast expression, and increased Treg cell expression. KGN revealed therapeutic activity with the potential to reduce pain and improve cartilage destruction. Thus, KGN could be a therapeutic molecule for OA that inhibits cartilage damage. |
format |
article |
author |
Ji Ye Kwon Seung Hoon Lee Hyun-Sik Na KyungAh Jung JeongWon Choi Keun Hyung Cho Chang-Yong Lee Seok Jung Kim Sung-Hwan Park Dong-Yun Shin Mi-La Cho |
author_facet |
Ji Ye Kwon Seung Hoon Lee Hyun-Sik Na KyungAh Jung JeongWon Choi Keun Hyung Cho Chang-Yong Lee Seok Jung Kim Sung-Hwan Park Dong-Yun Shin Mi-La Cho |
author_sort |
Ji Ye Kwon |
title |
Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10 |
title_short |
Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10 |
title_full |
Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10 |
title_fullStr |
Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10 |
title_full_unstemmed |
Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10 |
title_sort |
kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of il-10 |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/b046e22e941d47cb8e63906a174a3d14 |
work_keys_str_mv |
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