Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10

Scientific Reports

Chang-Yong Lee¹  Dong-Yun Shin¹  Seok Jung Kim²  KyungAh Jung³  Ji Ye Kwon⁴  Hyun-Sik Na⁴  Sung-Hwan Park⁴  Seung Hoon Lee⁴  Keun Hyung Cho⁴  JeongWon Choi⁴  Mi-La Cho⁴ 

[1] College of Pharmacy, Gachon University;Department of Orthopedic Surgery, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea;Impact Biotech, Korea 505 Banpo-Dong, Seocho-Ku;The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea;

关键词: Kartogenin (KGN);    Chondroclasts;    Treg Cell Differentiation;    Treg Cells;    Cartilage Destruction;   

DOI  :  10.1038/s41598-018-32206-7

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown