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

Med Sci Monit. 2019 Jul 4:25:4960-4967. doi: 10.12659/MSM.916696.

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 AND 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.

MeSH terms

  • Anilides / pharmacology*
  • Bone Morphogenetic Protein 7 / metabolism*
  • Cartilage / cytology
  • Cell Differentiation* / drug effects
  • Cell Proliferation / drug effects
  • Cell Shape
  • Chondrocytes / cytology*
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • HEK293 Cells
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Phthalic Acids / pharmacology*
  • Signal Transduction* / drug effects
  • Smad5 Protein / metabolism*
  • Synovial Membrane / cytology

Substances

  • Anilides
  • Bone Morphogenetic Protein 7
  • Phthalic Acids
  • Smad5 Protein
  • kartogenin