title: The PPARgamma-selective ligand BRL-49653 differentially regulates the fate choices of rat calvaria versus rat bone marrow stromal cell populations.
abstract: BACKGROUND
  Osteoblasts and adipocytes are derived from a common mesenchymal progenitor and an inverse relationship between expression of the two lineages is seen with certain experimental manipulations and in certain diseases, i.e., osteoporosis, but the cellular pathway(s) and developmental stages underlying the inverse relationship is still under active investigation. To determine which precursor mesenchymal cell types can differentiate into adipocytes, we compared the effects of BRL-49653 (BRL), a selective ligand for peroxisome proliferators-activated receptor (PPAR)gamma, a master transcription factor of adipogenesis, on osteo/adipogeneis in two different osteoblast culture models: the rat bone marrow (RBM) versus the fetal rat calvaria (RC) cell system.
  
  
  RESULTS
  BRL increased the number of adipocytes and corresponding marker expression, such as lipoprotein lipase, fatty acid-binding protein (aP2), and adipsin, in both culture models, but affected osteoblastogenesis only in RBM cultures, where a reciprocal decrease in bone nodule formation and osteoblast markers, e.g., osteopontin, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin was seen, and not in RC cell cultures. Even though adipocytes were histologically undetectable in RC cultures not treated with BRL, RC cells expressed PPAR and CCAAT/enhancer binding protein (C/EBP) mRNAs throughout osteoblast development and their expression was increased by BRL. Some single cell-derived BRL-treated osteogenic RC colonies were stained not only with ALP/von Kossa but also with oil red O and co-expressed the mature adipocyte marker adipsin and the mature osteoblast marker OCN, as well as PPAR and C/EBP mRNAs.
  
  
  CONCLUSIONS
  The data show that there are clear differences in the capacity of BRL to alter the fate choices of precursor cells in stromal (RBM) versus calvarial (RC) cell populations and that recruitment of adipocytes can occur from multiple precursor cell pools (committed preadipocyte pool, multi-/bipotential osteo-adipoprogenitor pool and conversion of osteoprogenitor cells or osteoblasts into adipocytes (transdifferentiation or plasticity)). They also show that mechanisms beyond activation of PPARgamma by its ligand are required for changing the fate of committed osteoprogenitor cells and/or osteoblasts into adipocytes.
authors.affiliation: 1Department of Orthodontics, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. hasetaku@hiroshima-u.ac.jp
authors.forename: Takuro
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Oizumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiko
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
authors.forename: Norihiko
authors.initials: N
authors.lastname: Maeda
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D008024:Ligands; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D000077154:Rosiglitazone; D012886:Skull; D017154:Stromal Cells; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone