Histone Demethylase KDM6B Promotes Chondrogenic Differentiation Potential of Stem Cells from the Apical Papilla Via HES1.

Abstract

Introduction: Mesenchymal stem cell (MSC)-based therapies have emerged as a promising approach for treating articular cartilage injuries. However, enhancing the chondrogenic differentiation potential of MSCs remains a significant challenge. KDM6B, a histone demethylase that specifically removes H3K27me3 marks, is essential in controlling the maturation of chondrocytes. In this study, we examined how KDM6B influences chondrogenic differentiation in SCAPs and investigated the underlying mechanisms involved.

Methods: SCAPs were utilized. Alcian Blue staining, pellet culture, and cell transplantation in rabbit knee cartilage defect models assessed MSC chondrogenic differentiation. Western blot, Real-time RT-PCR, and Microarray analysis examined the underlying molecular mechanisms.

Results: KDM6B promotes the expression of Aggrecan, COL2A1, COL5, glycosaminoglycans, and collagen fibers, while also increasing the COL2/COL1 ratio in SCAPs. In vivo, SCAPs overexpressing KDM6B significantly enhanced the repair and regeneration of knee cartilage and subchondral bone, with higher levels of glycosaminoglycan and COL5 expression observed within the tissue. KDM6B promotes the chondrogenic differentiation potential of SCAPs by repressing HES1. In addition, knock-down of HES1 enhanced the chondrogenic differentiation of SCAPs.

Conclusions: KDM6B enhances the differentiation of SCAPs into chondrocytes and demonstrated its effectiveness in the repair and regeneration of cartilage tissue and subchondral bone in vivo experiments. These findings provide an important foundation for future research on the use of dental tissue-derived stem cells to treat cartilage injuries.