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Background <p>Research on cartilage repair in the knee joint is crucial for treating knee arthritis or injuries. The application of mesenchymal stem cells (MSCs) for cartilage tissue regeneration represents a promising therapeutic approach. Among the critical aspects in cartilage formation, the enhancement of MSC chondrogenic differentiation stands as a pivotal challenge. WDR63 is a cytoplasmic dynein that plays a significant role in promoting stem cell differentiation and is closely associated with the cytoskeleton and energy metabolism processes. In the current study, our objective is to elucidate the phenotypic manifestations and mechanisms of WDR63 in relation to its chondrogenic differentiation function in MSCs.</p> Methods <p>Stem cells from apical papilla (SCAP) were used. The Alcian Blue staining technique, pellet culture system, and cell transplantation in rabbit knee cartilage defects were employed to assess the chondrogenic differentiation capabilities of MSCs. Western blot and real-time RT-PCR were utilized to investigate the molecular mechanisms involved.</p> Results <p>In vitro, WDR63 overexpression in SCAPs enhanced chondrogenic differentiation, as evidenced by upregulating collagen type II (<i>COL2</i>), collagen type V (<i>COL5</i>), and sex-determining region Y box protein 9 (<i>SOX9</i>), and robust pellet formation, whereas WDR63 knockdown produced opposite effects. In vivo, implantation of WDR63-overexpressing SCAP promoted cartilage repair in a rabbit osteochondral defect model, showing improved hyaline cartilage matrix deposition, higher COL2 expression, reduced collagen type X(COLX) expression, and increased collagen type Ι (COL1) expression in the subchondral bone. Mechanistically, WDR63 interacted and co-localized with vimentin (VIM), and its overexpression enhanced VIM expression and WDR63–VIM binding. WDR63 upregulates DRP1 expression, and rescues the Mdi-suppressed mitochondrial fission.</p> Conclusions <p>WDR63 may promote chondrogenic differentiation of SCAPs by interacting with VIM and enhancing its expression, potentially through facilitating mitochondrial fission.</p>

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WDR63 enhances the chondrogenic differentiation and regenerative potential of stem cell from apical papilla by facilitating vimentin function to promote mitochondrial fission

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月8日

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  • Jiawei Zhou,
  • Yangyang Cao,
  • Ziyan Sun,
  • Yishu Huang,
  • Mengyuan Zhu,
  • Zhipeng Fan

摘要

Background

Research on cartilage repair in the knee joint is crucial for treating knee arthritis or injuries. The application of mesenchymal stem cells (MSCs) for cartilage tissue regeneration represents a promising therapeutic approach. Among the critical aspects in cartilage formation, the enhancement of MSC chondrogenic differentiation stands as a pivotal challenge. WDR63 is a cytoplasmic dynein that plays a significant role in promoting stem cell differentiation and is closely associated with the cytoskeleton and energy metabolism processes. In the current study, our objective is to elucidate the phenotypic manifestations and mechanisms of WDR63 in relation to its chondrogenic differentiation function in MSCs.

Methods

Stem cells from apical papilla (SCAP) were used. The Alcian Blue staining technique, pellet culture system, and cell transplantation in rabbit knee cartilage defects were employed to assess the chondrogenic differentiation capabilities of MSCs. Western blot and real-time RT-PCR were utilized to investigate the molecular mechanisms involved.

Results

In vitro, WDR63 overexpression in SCAPs enhanced chondrogenic differentiation, as evidenced by upregulating collagen type II (COL2), collagen type V (COL5), and sex-determining region Y box protein 9 (SOX9), and robust pellet formation, whereas WDR63 knockdown produced opposite effects. In vivo, implantation of WDR63-overexpressing SCAP promoted cartilage repair in a rabbit osteochondral defect model, showing improved hyaline cartilage matrix deposition, higher COL2 expression, reduced collagen type X(COLX) expression, and increased collagen type Ι (COL1) expression in the subchondral bone. Mechanistically, WDR63 interacted and co-localized with vimentin (VIM), and its overexpression enhanced VIM expression and WDR63–VIM binding. WDR63 upregulates DRP1 expression, and rescues the Mdi-suppressed mitochondrial fission.

Conclusions

WDR63 may promote chondrogenic differentiation of SCAPs by interacting with VIM and enhancing its expression, potentially through facilitating mitochondrial fission.