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 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.

Identification of the Key Role of NF-κB Signaling Pathway in the Treatment of Osteoarthritis With Bushen Zhuangjin Decoction, a Verification Based on Network Pharmacology Approach

“…Osteoarthritis (OA) is common in the aging population. It has been regarded as a severe public health concern since it remarkably reduces quality of life (Ashraf et al, 2018;Kwon et al, 2018). The mechanisms of OA are complicated and not fully understood.…”

Cartilage Extracellular Matrix Scaffold With Kartogenin-Encapsulated PLGA Microspheres for Cartilage Regeneration

“…Furthermore, KGN has protective effects with respect to existing cartilage tissue and reduces the decomposition of chondrogenic proteins; thus, it slows the progression of cartilage injury ( Cai et al, 2019 ). Although KGN has been investigated as a cartilage-promoting molecule, two common models of KGN application remain problematic: (1) direct injection into the joint cavity, ( Xu et al, 2015 ; Kwon et al, 2018 ) which is ineffective because most KGN is absorbed by the circulatory system and repeated injections increase both pain and risk of infection; (2) combination of KGN with drug delivery system: such as hydrogel ( Wang S.J. et al, 2019 ), platelet-rich plasma (PRP)( Liu et al, 2019 ), nanoparticles, or microspheres ( Kang et al, 2014 ).…”

Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration

“…Based on this evidence, KGN might possibly be more specific in terms of cartilage differentiation of MSCs and could be a proper alternative to chondrogenic growth factors. Recently, Kwon et al reported that KGN treatment could induce IL-10 production and showed protective activity against cartilage degeneration through downregulation of matrix metalloproteinases (MMPs), MMP3 and MMP6, and inflammatory agents such as IL-6, TNF-α, and IL-1β [41].…”