Abstract
Chondrocytes and adipocytes are two differentiated cell types which are both derived from mesenchymal cells. The purpose of this study was to investigate whether peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor involved in lineage determination during adipogenesis, is able to induce adipogenic differentiation in growth plate chondrocytes. Isolated epiphyseal chondrocytes were infected with a PPARγ adenovirus or treated with the PPARγ agonist ciglitazone. Both of these treatments resulted in lipid droplet accumulation and expression of the adipogenic markers aP2, lipoprotein lipase, and adipsin in chondrocytes. Proteoglycan matrix synthesis was decreased in the PPARγ-infected cells, as was the expression of the chondrogenic genes Col2a1 and aggrecan. Growth plate cells transfected with a PPARγ expression plasmid under the control of the collagen α1(II) promoter also demonstrated a similar adipogenic changes. Terminal differentiation of growth plate chondrocytes induced by thyroid hormone was also inhibited by overexpression of PPARγ and ciglitazone treatment, with decreased expression of alkaline phosphatase and Runx2/Cbfa1 genes. These in vitro data suggest that PPARγ is able to promote adipogenic differentiation in growth plate chondrocytes, while negatively regulating chondrogenic differentiation and terminal differentiation.
Highlights
Longitudinal growth of the skeleton is a result of endochondral ossification that occurs at the growth plate [1]
Based on the finding that peroxisome proliferator-activated receptor-γ (PPARγ) is expressed in growth plate chondrocytes [10], as well as the evidence that PPARγ is able to compete with the thyroid hormone receptor (TR) for binding to retinoic acid receptor X to inhibit growth plate cell hypertrophy [11], the purpose of this study was to PPAR Research investigate whether PPARγ and its ligands are able to promote adipogenic differentiation and suppress chondrogenic differentiation in growth plate chondrocytes
Treatment of growth plate cells with ciglitazone resulted in increases of both PPARγ mRNA and protein
Summary
Longitudinal growth of the skeleton is a result of endochondral ossification that occurs at the growth plate [1]. Endochondral ossification is a multistep process that includes differentiation of mesenchymal cells into chondrocytes, cell proliferation, hypertrophic differentiation, matrix mineralization, apoptosis, vascular invasion, and eventually the replacement of the cartilage by bone. Mesenchymal stem cells exhibit a high differentiation plasticity. They are capable of differentiating into chondrocytes, osteoblasts, adipocytes, and other tissues of mesenchymal origin [2]. Interconversion between mesenchymal phenotypes is thought to be under control of specific transcription factors, including the Sox family in chondrogenesis [3], Runx2/Cbfa in osteogenesis [4], and PPARγ (peroxisome proliferator-activated receptor-γ), and C/EBP (CCAAT/enhancer-binding protein) in adipogenesis [5]
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