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

Abstract

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.

Review of Ortho-Biologics in Rotator Cuff Repair

“…In vitro studies of BMP-2 and 7 have demonstrated dose dependent increases in type I collagen production, expression and cellular activity [22,23]. Further in vitro study of BMP-7 has shown that it can induce differentiation of mesenchymal stem cells into chondrocytes which promotes the regeneration of interfacial cartilage and improves the quality of tendon healing [24]. In both rabbit and rat models, BMP-2 and 7 have demonstrated the ability to enhance new bone formation and tensile strength in repaired tendon insertions [24][25][26].…”

“…Further in vitro study of BMP-7 has shown that it can induce differentiation of mesenchymal stem cells into chondrocytes which promotes the regeneration of interfacial cartilage and improves the quality of tendon healing [24]. In both rabbit and rat models, BMP-2 and 7 have demonstrated the ability to enhance new bone formation and tensile strength in repaired tendon insertions [24][25][26]. Unfortunately, no studies have been published on the use of BMP-2 or 7 in human RCR.…”

Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone

“…In diarthrodial joints, which allow a large degree of movement, the surfaces of the opposing bones are lined with hyaline cartilage, which reduces friction [ 89 ]. Chondrocytes are derived from MSCs [ 90 ]. Chondrocytes experience a complex mechanical environment and respond to changing mechanical loads in order to maintain cartilage homeostasis [ 91 ].…”

Recent Developed Strategies for Enhancing Chondrogenic Differentiation of MSC: Impact on MSC-Based Therapy for Cartilage Regeneration

“…In addition, the combination of KGN and TGF- β 3 has synergistic effects, as human umbilical cord-derived mesenchymal stem cells (UCMSCs) treated with KGN and TGF- β 3 were shown to secrete more COL II than MSCs treated with TGF- β 3 or KGN alone [ 31 ]. Zhou et al reported that KGN can induce the differentiation of human SDSCs (hSDSCs) into chondrocytes through the activation of the BMP-7/Smad5 signaling pathway [ 32 ]. In addition, Jing et al revealed that human UCMSCs (hUCMSCs) preconditioned with KGN were stalled in a precartilaginous stage with the activation of JNK/RUNX1 pathway and suppression of β -catenin/RUNX2 pathway [ 33 ].…”