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Impact of targeted PPARγ disruption on bone remodeling

Jay Cao1, Guomin Ou2, Nianlan Yang2

  • 1USDA ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States.

Molecular and Cellular Endocrinology
|February 11, 2015
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPARγ) deletion in bone cells increases osteoblasts, aiding bone repair. This study clarifies PPARγ’s role in bone remodeling, not skeletal development.

Area of Science:

  • Bone Biology
  • Stem Cell Biology
  • Endocrinology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARγ) regulates adipogenesis and is a potential therapeutic target for osteoporosis.
  • The exact role of PPARγ in bone regulation is unclear due to confounding effects from other tissues.
  • A bone-specific PPARγ conditional knockout (cKO) model is needed to elucidate its precise function in bone.

Purpose of the Study:

  • To investigate the specific role of PPARγ in bone biology using a bone-specific cKO mouse model.
  • To determine the effect of PPARγ deletion on bone marrow mesenchymal stem/progenitor cell (BMSC) lineage commitment.
  • To clarify the mechanism by which PPARγ influences bone remodeling and skeletal development.

Main Methods:

  • Generated bone-specific PPARγ cKO mice (PPAR(fl/fl):Col3.6-Cre).
  • Performed in vitro studies on primary bone marrow cultures and isolated BMSCs.
  • Conducted histology and histomorphometry analyses on cKO mice.
  • Assessed osteoclast differentiation and function.

Main Results:

  • PPARγ cKO mice exhibited a moderate, site-dependent decrease in bone mass.
  • In vitro, adipogenesis was abolished, and osteoblastogenesis was significantly increased in PPARγ-deficient cells.
  • Histomorphometry revealed increased osteoblast numbers and surface in cKO mice.
  • Osteoclast differentiation and function remained unaffected.

Conclusions:

  • PPARγ plays a crucial role in bone remodeling by promoting osteoblast abundance for repair.
  • PPARγ is not essential for skeletal development.
  • Targeting PPARγ may offer a therapeutic strategy for bone repair in conditions like osteoporosis.
Keywords:
AgingBone lossMSCOsteoblastsPPARγ

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