Neuropeptide Y modulates fracture healing through Y1 receptor signaling

Daniela M Sousa1, Michelle M McDonald, Kathy Mikulec

  • 1Instituto de Engenharia Biomédica (INEB), NEWTherapies Group, Universidade do Porto, Porto, Portugal.

Insights

Global deletion of the Neuropeptide Y receptor Y1 (Y1 (-/-)) delays fracture healing in mice. This impairment involves reduced callus volume, strength, and delayed cartilage removal, impacting bone regeneration.

Area of Science:

  • Bone biology
  • Endocrinology
  • Regenerative medicine

Background:

  • Neuropeptide Y (NPY) signaling via its Y1 receptor influences bone mass.
  • Previous studies showed Y1 receptor deletion promotes bone anabolism.
  • The role of Y1 receptor in fracture healing was previously unclear.

Purpose of the Study:

  • To investigate the role of Y1 receptor deletion in fracture healing.
  • To characterize the effects of global and osteoblast-specific Y1 receptor knockout on tibial fracture repair.

Main Methods:

  • Induction of closed tibial fractures in germline (Y1 (-/-)) and osteoblast-specific Y1 receptor knockout mice.
  • Monitoring fracture repair progression from 1 to 6 weeks post-fracture.
  • Assessment of bone callus volume, strength, and histological features.

Main Results:

  • Global Y1 receptor deletion (Y1 (-/-)) significantly delayed fracture repair.
  • Y1 (-/-) mice exhibited decreased bone callus volume and strength.
  • Histological analysis revealed increased avascular and cartilage areas, with delayed cartilage resorption, indicating impaired union.
  • The delay was not attributed to Y1 receptors in mature osteoblasts.

Conclusions:

  • Global absence of the Y1 receptor impairs fracture healing by disrupting early repair phases.
  • Y1 receptor signaling is crucial for timely bone regeneration and achieving bony union.
  • Understanding Y1 receptor's role in bone repair can inform future therapeutic strategies for bone regeneration.

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