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Skeletal phenotype of the neuropeptide Y knockout mouse

Natalie K Y Wee1, Benjamin P Sinder1, Sanja Novak1

  • 1Department of Reconstructive Sciences, Farmington, CT 06030, USA.

Neuropeptides
|December 8, 2018
PubMed

Insights

Neuropeptide Y (NPY) depletion reduces bone strength in male mice and enhances osteogenic differentiation in bone marrow stromal cells. NPY

Area of Science:

  • Skeletal biology and metabolism
  • Neuroendocrinology
  • CRISPR gene editing

Background:

  • Neuropeptide Y (NPY) influences behavior, energy, and bone metabolism.
  • Previous studies used global NPY depletion, obscuring central vs. local NPY effects on bone.
  • Identifying skeletal NPY sources is crucial for understanding bone regulation.

Purpose of the Study:

  • To identify skeletal cells expressing Npy.
  • To create a model for differentiating NPY effects from various cell types.
  • To investigate the impact of global NPY depletion on bone metabolism.

Main Methods:

  • Generated NPY floxed (NPYflox) mice using CRISPR technology.
  • Created global NPY knockout (NPYKO) mice by crossing NPYflox with Hprt-cre mice.
  • Validated Npy transcript and protein loss in NPYKO mice.
  • Assessed bone parameters (femoral cross-sectional area, bone strength) and in vitro osteogenic differentiation of bone marrow stromal cells (BMSCs).

Main Results:

  • Global NPY deletion resulted in a 12% smaller femoral cortical cross-sectional area and an 18% reduction in bone strength in male mice.
  • NPY-deficient BMSCs exhibited increased osteogenic differentiation.
  • Both sexes showed increased adiposity, but only male mice had altered bone mass, suggesting sex-specific NPY effects.
  • Npy expression was identified within the skeleton.

Conclusions:

  • NPY plays a role in regulating bone mass and strength, with potential sex-specific effects.
  • NPY signaling in bone is complex, with distinct sources influencing different skeletal compartments.
  • The NPYflox mouse model enables future dissection of NPY's cell-specific roles in bone.
  • Further research is needed to elucidate the precise mechanisms and sources of NPY action in bone metabolism.
Keywords:
BoneBone strengthConditional mouseCortical boneNeuropeptide Y (NPY)

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