Abstract
BackgroundOsteoblasts 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)γ, 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.ResultsBRL 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.ConclusionThe 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 PPARγ by its ligand are required for changing the fate of committed osteoprogenitor cells and/or osteoblasts into adipocytes.
Highlights
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 whether there is a difference in the effects of BRL on osteoblastogenesis between these two models, we first assessed the number of bone nodules and adipocyte colonies in rat bone marrow (RBM) versus rat calvaria (RC) cell cultures treated with BRL (Fig. 1A and 1B)
In BRL-treated single cell colonies, mineralized colonies with and without adipsin expression (Fig. 5B) correlated with high and low levels of PPARγ respectively, which is consistent with the hypothesis that RC cell populations comprise two kinds or differentiation stages of progenitor or osteoblastic cells as we described previously with respect to glucocorticoid regulation [29,30], i.e., a subpopulation responsive to the PPARγ selective ligand and a non-responsive subpopulation, with the former capable of expressing both the adipocyte and osteoblast programs and the latter expressing only the osteoblast program
Summary
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. Osteoblasts and adipocytes derive from a common mesenchymal progenitor and appear to display plasticity between the phenotypes and an inverse relationship between expression of the two lineages under certain pathological and several experimental conditions [1]. As summarized previously [5], it can often be difficult to interpret the developmental and cellular basis of the inverse relationship between osteoblasts and adipocytes, when both bi-/multipotential progenitors reside in the same populations as restricted monopotential progenitors that may display plasticity or transdifferentiation capacity. Specific treatments and different culture conditions including different cell densities may dependently or independently affect any or all of these lineage choices
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