ROR2 Downregulation Activates the MSX2/NSUN2/p21 Regulatory Axis and Promotes Dental Pulp Stem Cell Senescence

Xin He1, Zhan Yang2, Xiao-Yang Chu3

  • 1Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, People's Republic of China.

Insights

Cellular senescence in dental pulp stem cells (DPSCs) is linked to ROR2 and MSX2. Targeting the ROR2/MSX2/NSUN2 pathway can inhibit DPSC aging and restore self-renewal capacity.

Area of Science:

  • Stem cell biology
  • Molecular and cellular biology
  • Regenerative medicine

Background:

  • Cellular senescence limits dental pulp stem cell (DPSC) research and applications.
  • ROR2 is implicated in DPSC senescence, but the regulatory mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism of ROR2 regulation in DPSC senescence.
  • To identify potential targets for antagonizing DPSC aging.

Main Methods:

  • Investigated MSX2 expression in aging DPSCs.
  • Performed MSX2 depletion and ROR2 overexpression experiments.
  • Analyzed the ROR2/MSX2/NSUN2/p21 axis in DPSC senescence.

Main Results:

  • MSX2 expression increased in aging DPSCs.
  • MSX2 depletion inhibited DPSC senescence and restored self-renewal.
  • The ROR2/MSX2/NSUN2 axis was identified as a key regulator of DPSC aging.
  • ROR2 downregulation affected MSX2 protein levels by altering phosphorylation and ubiquitination.

Conclusions:

  • The ROR2/MSX2/NSUN2 axis plays a vital role in regulating DPSC senescence.
  • This pathway represents a potential therapeutic target for combating DPSC aging.

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