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Activation of peroxisome proliferator-activated receptor-gamma pathway inhibits osteoclast differentiation

G Mbalaviele1, Y Abu-Amer, A Meng

  • 1Osiris Therapeutics, Inc., Baltimore, Maryland 21231, USA. gmbalaviele@osiristx.com

The Journal of Biological Chemistry
|May 9, 2000
PubMed

Insights

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) pathway inhibits osteoclast formation. This finding links PPAR-gamma signaling to osteoclast differentiation, impacting bone remodeling and related diseases.

Area of Science:

  • * Molecular biology
  • * Cell biology
  • * Immunology

Background:

  • * Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor regulating adipogenesis and inflammation.
  • * Osteoclast (Ocl) formation is crucial for bone remodeling and is influenced by various signaling pathways.

Purpose of the Study:

  • * To investigate the role of the PPAR-gamma pathway in osteoclast formation from CD34(+) hematopoietic stem cells (HSCs).
  • * To elucidate the interaction between PPAR-gamma and osteoprotegerin ligand (OPGL) signaling in osteoclastogenesis.

Main Methods:

  • * Co-culture system using human mesenchymal stem cells (hMSCs) and CD34(+) HSCs.
  • * Stimulation of osteoclast formation with soluble OPGL (sOPGL) and macrophage-colony stimulating factor (M-CSF).
  • * Treatment with 15-deoxy-Delta(12, 14)-prostaglandin-J2 (15d-PG-J2), a PPAR-gamma agonist, to assess its inhibitory effects.

Main Results:

  • * sOPGL and M-CSF significantly enhanced osteoclast formation in co-cultures.
  • * CD34(+) HSCs express PPAR-gamma, while hMSCs do not.
  • * 15d-PG-J2 completely inhibited sOPGL and M-CSF-induced osteoclast formation and activity, specifically in the osteoclast lineage.
  • * sOPGL-induced activation of the NF-kappaB pathway in osteoclast progenitors was abolished by 15d-PG-J2.

Conclusions:

  • * The PPAR-gamma pathway plays a significant role in modulating osteoclastogenesis.
  • * A direct link exists between PPAR-gamma and OPGL signaling in osteoclast progenitors.
  • * PPAR-gamma agonists may represent a therapeutic target for conditions involving excessive osteoclast activity.

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