Cultured human periosteal-derived cells have inducible adipogenic activity and can also differentiate into osteoblasts in a perioxisome proliferator-activated receptor-mediated fashion

Int J Med Sci. 2014 Aug 16;11(11):1116-28. doi: 10.7150/ijms.9611. eCollection 2014.

Abstract

We investigated the adipogenic activity of cultured human periosteal-derived cells and studied perioxisome proliferator-activated receptor (PPAR) ligand-mediated differentiation of cultured human periosteal-derived cells into osteoblasts. Periosteal-derived cells expressed adipogenic markers, including CCAAT/enhancer binding protein α (C/EBP- α), C/EBP-δ, aP2, leptin, LPL, and PPARγ. Lipid vesicles were formed in the cytoplasm of periosteal-derived cells. Thus, periosteal-derived cells have potential adipogenic activity. The PPARα and PPARγ agonists, WY14643 and pioglitazone, respectively, did not modulate alkaline phosphatase (ALP) activity in periosteal-derived cells during induced osteoblastic differentiation, however, the PPARα and PPARγ antagonists, GW6471 and T0070907, respectively, both decreased ALP activity in these cells. WY14643 did not affect, whereas pioglitazone enhanced, alizarin red-positive mineralization and calcium content in the periosteal-derived cells. GW6471 and T0070907 both decreased mineralization and calcium content. By RT-PCR, pioglitazone significantly increased ALP expression in periosteal-derived cells between culture day 3 and 2 weeks. Pioglitazone increased Runx2 expression after 3 days, which declined thereafter, but did not alter osteocalcin expression. Both of GW6471 and T0070907 decreased ALP mRNA expression. These results suggest that pioglitazone enhances osteoblastic differentiation of periosteal-derived cells by increasing Runx2 and ALP mRNA expression, and increasing mineralization. GW6471 and T0070907 inhibit osteoblastic differentiation of the periosteal-derived cells by decreasing ALP expression and mineralization in the periosteal-derived cells. In conclusion, although further study will be needed to clarify the mechanisms of PPAR-regulated osteogenesis, our results suggest that PPARγ agonist stimulates osteoblastic differentiation of cultured human periosteal-derived cells and PPARα and PPARγ antagonists inhibit osteoblastic differentiation in these cells.

Keywords: Adipogenic activity; Osteoblastic differentiation; PPAR ligands.; Periosteal-derived cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Humans
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Oxazoles / pharmacology
  • PPAR alpha / agonists
  • PPAR alpha / antagonists & inhibitors
  • PPAR gamma / agonists
  • PPAR gamma / antagonists & inhibitors
  • Periosteum / cytology*
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Peroxisome Proliferator-Activated Receptors / antagonists & inhibitors
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Pioglitazone
  • Pyridines / pharmacology
  • Pyrimidines / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiazolidinediones / pharmacology
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology

Substances

  • Benzamides
  • GW 6471
  • Oxazoles
  • PPAR alpha
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptors
  • Pyridines
  • Pyrimidines
  • T 0070907
  • Thiazolidinediones
  • Tyrosine
  • pirinixic acid
  • Pioglitazone