Application of kartogenin for musculoskeletal regeneration

Im, Gun‐Il

doi:10.1002/jbm.a.36300

Cited by 28 publications

(22 citation statements)

References 26 publications

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“…Kartogenin, a small bioactive compound made of 22,000 structurally diverse, heterocyclic small molecules, 2 can promote the differentiation of the stem cells into chondrocytes and enhance cartilage regeneration. 3 However, in the present study, the authors indicated that higher percentages of the fibrocartilage formation were found in the control group than that in the kartogenin-treated group. This result differs from published findings.…”

Section: See Related Article On Page 2579contrasting

confidence: 71%

Editorial Commentary: Kartogenin Promotes Wounded Enthesis Regeneration

Huang

2018

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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Section: See Related Article On Page 2579contrasting

confidence: 71%

Editorial Commentary: Kartogenin Promotes Wounded Enthesis Regeneration

Huang

2018

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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“…Kartogenin (KGN), a heterocyclic-structured smallmolecule compound, can promote the chondrogenic differentiation of MSCs and protect chondrocytes from ossification (12). The applications of KGN in tissue engineering and regenerative medicine have been widely expanded since its discovery, including musculoskeletal, meniscal, and articular cartilaginous regeneration strategies (13)(14)(15). However, the efficiency of chondrogenesis induced by KGN alone has been far from satisfactory, impeding its further clinical application (16,17).…”

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confidence: 99%

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

et al. 2019

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Cartilage engineering strategies using mesenchymal stem cells (MSCs) could provide preferable solutions to resolve long‐segment tracheal defects. However, the drawbacks of widely used chondrogenic protocols containing TGF‐β3, such as inefficiency and unstable cellular phenotype, are problematic. In our research, to optimize the chondrogenic differentiation of human umbilical cord MSCs (hUCMSCs), kartogenin (KGN) preconditioning was performed prior to TGF‐β3 induction. hUCMSCs were preconditioned with 1 µM of KGN for 3 d, sequentially pelleted, and incubated with TGF‐β3 for 28 d. Then, the expression of chondrogenesis‐ and ossification‐related genes was evaluated by immunohistochemistry and RT‐PCR. The underlying mechanism governing the beneficial effects of KGN preconditioning was explored by phosphorylated kinase screening and validated in vitro and in vivo using JNK inhibitor (SP600125) and β‐catenin activator (SKL2001). After KGN preconditioning, expression of fibroblast growth factor receptor 3, a marker of precartilaginous stem cells, was up‐regulated in hUCMSCs. Furthermore, the KGN‐preconditioned hUCMSCs efficiently differentiated into chondrocytes with elevated chondrogenic gene (SOX9, aggrecan, and collagen II) expression and reduced expression of ossifie genes (collagen X and MMP13) compared with hUCMSCs treated with TGF‐β3 only. Phosphokinase screening indicated that the beneficial effects of KGN preconditioning are directly related to an up‐regulation of JNK phosphorylation and a suppression of β‐catenin levels. Blocking and activating tests revealed that the prochondrogenic effects of KGN preconditioning was achieved mainly by activating the JNK/Runt‐related transcription factor (RUNX)1 pathway, and antiossific effects were imparted by suppressing the β‐catenin/RUNX2 pathway. Eventually, tracheal patches, based on KGN‐preconditioned hUCMSCs and TGF‐β3 encapsulated electrospun poly (l‐lactic acid‐co‐ε‐caprolactone)/collagen nanofilms, were successfully used for restoring tracheal defects in rabbit models. In summary, KGN preconditioning likely improves the chondrogenic differentiation of hUCMSCs by committing them to a precartilaginous stage with enhanced JNK phosphorylation and suppressed β‐catenin. This novel protocol consisting of KGN preconditioning and subsequent TGF‐β3 induction might be preferable for cartilage engineering strategies using MSCs.—Jing, H., Zhang, X., Gao, M., Luo, K., Fu, W., Yin, M., Wang, W., Zhu, Z., Zheng, J., He, X. Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin—related pathways. FASEB J. 33, 5641–5653 (2019). http://www.fasebj.org

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“…Kartogenin (KGN) is a recently characterized drug with small molecule that promotes the selective differentiation of endogenous MSCs into chondrocytes, thus stimulating cartilage regeneration [10]. In addition, limb skeletal growth and tendon development both can be enhanced by KGN [11,12].…”

Section: Introductionmentioning

confidence: 99%

A New Insight of Kartogenin Induced the Mesenchymal Stem Cells (MSCs) Selectively Differentiate into Chondrocytes by Activating the Bone Morphogenetic Protein 7 (BMP-7)/Smad5 Pathway

et al. 2019

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Background Rotator cuff injury is the most common cause of shoulder disability, and although the repair technique has improved, the rate of rotator cuff reduction after repair is still high. The fibrocartilage region, which appears to be histologically inserted, cannot be regenerated. In recent years, studies have reported that mesenchymal stem cells (MSCs) have enhanced cartilage regeneration in the tendon and bone interface after rotator cuff repair, which has become a hot topic of research. Material/Methods Two mesenchymal stem cell types, SMSC (synovial-derived mesenchymal stem cells) and BMSC (bone marrow-derived mesenchymal stem cells) were intervened using kartogenin (KGN). The cytotoxicity was evaluated and the proliferation of the 2 cells was observed. Four commonly used cartilage phenotype genes were detected by quantitative real-time polymerase chain reaction, and the cartilage differentiation of MSCs induced by KGN was explored. The bidirectional regulation of the expression of BMP-7 and the downstream gene Smad5 was observed by constructing a lentiviral overexpression vector containing the target gene BMP-7. To explore whether BMP-7/Smad5 pathway activation promotes differentiation of SMSCs into chondrocytes. Results KGN can induce the selective differentiation of endogenous MSCs into chondrocytes by activating the BMP-7/Smad5 pathway, which promotes the regeneration of interfacial cartilage, and improves the quality of tendon healing of the tendon after rotator cuff repair. Conclusions This study found a new biological intervention method to promote the effect of tendon on bone healing after rotator cuff repair.

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Application of kartogenin for musculoskeletal regeneration

Cited by 28 publications

References 26 publications

Editorial Commentary: Kartogenin Promotes Wounded Enthesis Regeneration

Editorial Commentary: Kartogenin Promotes Wounded Enthesis Regeneration

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

A New Insight of Kartogenin Induced the Mesenchymal Stem Cells (MSCs) Selectively Differentiate into Chondrocytes by Activating the Bone Morphogenetic Protein 7 (BMP-7)/Smad5 Pathway

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