Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

Abstract

We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with TGFβ1 during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rhTGFβ1 synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization.

Role of ALK5/Smad2/3 and MEK1/ERK Signaling in Transforming Growth Factor Beta 1–modulated Growth, Collagen Turnover, and Differentiation of Stem Cells from Apical Papilla of Human Tooth

“…Recently, Yang et al (44) also found that transfection of TGF-b1 to SCAPs may induce a number of mineral-related gene expressions. Similar stimulation of ALP at a lower TGF-b1 concentration and inhibition of ALP at a higher concentration is also noted in osteoblasts (45)(46)(47)(48) and pulp cells (data not shown) (31). However, TGF-b1 was found to inhibit the ALP activity of SCAPs cultured in mineralizing differentiation medium (36).…”

“…In this study, proliferation of SCAP resulted under both low and high concentrations of TGF-b1, but the ALP activity was stimulated under low TGF-b1 and suppressed under high concentrations of TGF-b1. Although the precise reasons are still not fully clarified, the differential effects of TGF-b are suggested to be related to concentration, cell types, method of cell isolation, cell passages, cell density, cell differentiation/maturation status, the expression of type II and III TGF-b receptors, differential signaling pathways, extracellular matrix, and culture conditions (eg, the timing and duration of exposure and costimulation by other growth factors in differentiated medium) (36,(45)(46)(47)(48)(52)(53)(54).…”

Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing

“…Protein extraction and western blotting was performed as previously described (16). To extract total proteins, cells treated with DMEM, AdGFP or AdBMP9 for 2 or 7 days were washed with cold PBS (4°C) and lysed in 300 µl RIPA lysis buffer (Sigma-Aldrich; Merck Millipore).…”

The potential of mesenchymal stem cells derived from amniotic membrane and amniotic fluid for neuronal regenerative therapy

“…MSCs can be multipotent and differentiated into various cell types, not only mecenchymal lineage cells, such as chondrocytes, adipocytes, osteocytes, but also nonmesodermal lineage, such as epithelial cells, hepatocyte cells, cardiomyocyte cells, insulin secreting pancreatic β-cells, and neuronal cells (4-9). In addition, MSCs have several advantages, including their nontumorigenicity and anti-immunogenic activity and minimal ethical problems compared with any other candidates for regenerative therapy.…”