Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A

Abstract

The pluripotent mesenchymal stem cells give rise to osteoblasts, adipocytes, chondrocytes, and myoblasts. The differentiation of these stem cells into each of the mature functional cells may be controlled by a distinctive master gene(s) and is associated with temporal and spatial expression of diverse genes. Identification of genes that are expressed during the differentiation of the mesenchymal cells to osteoblasts is, therefore, important to obtain insights into the molecular mechanisms of osteogenesis. The murine undifferentiated mesenchymal cell 3T3-F442A, when treated with the bone morphogenetic protein 2 (BMP-2), a well-characterized inducer of mesenchymal cell differentiation, exhibited both osteoblastic and adipocytic differentiation. Using the SAGE (serial analysis of gene expression) technique, which has been shown to enable quantitative analysis of large numbers of genes in a simple and quick manner, we obtained 1600 sequence tags representing 2107 individual nucleotide sequences from control and BMP-2-treated 3T3-F442A cells, respectively. By comparing the frequency of tag occurrence, we found profiles of up- or downregulated genes associated with osteoblast or adipocyte phenotype such as type I collagen, osteonectin and OSF-2, or C/EBPbeta, aP2, fatty acid synthase, and lipoprotein lipase, respectively, in BMP-2-treated 3T3-F442A cells. Our data show that BMP-2 induces not only osteoblastic but also adipocytic differentiation in the 3T3-F442A cells. They also show that the 3T3-F442A cells have bipotentials of differentiating toward osteoblasts and adipocytes. The results, therefore, might explain the inverse correlation between trabecular bone volume and fat volume in the bone marrow cavity. The results also suggest that the SAGE may be a useful technique that allows us a fast and efficient way to generate global and local views of gene expression associated with cellular differentiation of the mesenchymal stem cells.

Immunolocalization of chick periostin protein in the developing heart

“…This hypothesis is consistent with the cells of the tooth mesenchyme that also highly express periostin and undergo an EMT (Kruzynska-Frejtag et al, 2004). During cardiovascular development initially, periostin is expressed in response to signaling from the BMP and TGF-␤ family of growth factors (Horiuchi et al, 1999;Ji et al, 2000;Hall et al, 2001;Kruzynska-Frejtag et al, 2001Lindner et al, 2004). However, as development progresses, the heart must withstand the increasing influence of hemodynamic sheer stress (Stekelenburg et al, 2004).…”

“…These mesenchymal precursors may undergo apoptosis to create and enlarge the extracellular spaces that precede delamination and/or transdifferentiate into cells that form the tendinous cords of the valvular suspensory apparatus. Since these mesenchymal cells have been shown to have the potential to form a diverse population of differentiated cells such as cardiac muscle, cartilage, bone, and bone marrow (Icardo, 1989b;Galvin et al, 2000), the expression of periostin at later stages in valvulogenesis may serve to maintain the fibrous or tendinous identity of these cells (Ji et al, 2000). We have shown that early in cardiac cushion formation, periostin is associated in fibrous strands long before the differentiated fibrous tissues could be identified within the forming valves.…”

“…Initially thought to be bone-specific and required for osteoblast differentiation, subsequent experiments revealed that OSF-2 expression diminished as osteoblasts became committed to the bone lineage. Additional studies went on to show the antiosteogenic function of this molecule (Hall and Miyake, 2000;Ji et al, 2000;Saito et al, 2002). OSF-2 was found to be strongly expressed in the periodontal ligament (PDL), the periosteium, endocardial cushions and valves of the developing heart and was renamed periostin (Horiuchi et al, 1999;Kruzynska-Frejtag et al, 2001;Wilde et al, 2003).…”

“…Periostin expression is significantly increased in response to BMP and TGF-␤ growth factor signaling in mesenchymal cells undergoing differentiation (Horiuchi et al, 1999;Ji et al, 2000). In the heart, BMP and TGF-␤ are secreted by the myocardium and stimulate the endocardial cushions during growth and development (Eisenberg and Markwald, 1995;Nakajima et al, 1997Nakajima et al, , 2000Sugi et al, 2004).…”

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

“…Additionally, periostin interacts with structural collagens, thereby influencing mechanical properties of the ECM (Gillan et al, 2002; Kudo, 2011; Norris et al, 2007). Its expression is controlled by mechanical stimuli and growth factors, such as transforming growth factor beta, bone morphogenetic protein 2, among other signaling molecules (Aukkarasongsup, Haruyama, Matsumoto, Shiga, & Moriyama, 2013; Ji et al, 2000). …”