TY - JOUR
T1 - BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium-derived progenitor cells cultured in three-dimensional alginate hydrogel
AU - Park, Y.
AU - Sugimoto, M.
AU - Watrin, A.
AU - Chiquet, M.
AU - Hunziker, Ernst B.
N1 - Funding Information:
This project was supported by the Swiss National Science Foundation, Bern, Switzerland, and by the Novartis Foundation, Basel, Switzerland (grants to EBH).
PY - 2005/6
Y1 - 2005/6
N2 - Objective: According to recent reports, the synovial membrane may contain mesenchymal stem cells with the potential to differentiate into chondrocytes under appropriate conditions. In order to assess the usefulness of synovium-derived progenitor cells for the purposes of cartilage tissue engineering, we explored their requirements for the expression of chondrocyte-specific genes after expansion in vitro. Design: Mesenchymal progenitor cells were isolated from the synovial membranes of bovine shoulder joints and expanded in two-dimensions on plastic surfaces. They were then seeded either as micromass cultures or as single cells within alginate gels, which were cultured in serum-free medium. Under these three-dimensional conditions, chondrogenesis is known to be supported and maintained. Cell cultures were exposed either to bone morphogenetic protein-2 (BMP-2) or to isoforms of transforming growth factor-β (TGF-β). The levels of mRNA for Sox9, collagen types I and II and aggrecan were determined by RT-PCR. Results: When transferred to alginate gel cultures, the fibroblast-like synovial cells assumed a rounded form. BMP-2, but not isoforms of TGF-β, stimulated, in a dose-dependent manner, the production of messenger RNAs (mRNAs) for Sox9, type II collagen and aggrecan. Under optimal conditions, the expression levels of cartilage-specific genes were comparable to those within cultured articular cartilage chondrocytes. However, in contrast to cultured articular cartilage chondrocytes, synovial cells exposed to BMP-2 continued to express the mRNA for α1(I) collagen. Conclusions: This study demonstrates that bovine synovium-derived mesenchymal progenitor cells can be induced to express chondrocyte-specific genes. However, the differentiation process is not complete under the chosen conditions. The stimulation conditions required for full transformation must now be delineated.
AB - Objective: According to recent reports, the synovial membrane may contain mesenchymal stem cells with the potential to differentiate into chondrocytes under appropriate conditions. In order to assess the usefulness of synovium-derived progenitor cells for the purposes of cartilage tissue engineering, we explored their requirements for the expression of chondrocyte-specific genes after expansion in vitro. Design: Mesenchymal progenitor cells were isolated from the synovial membranes of bovine shoulder joints and expanded in two-dimensions on plastic surfaces. They were then seeded either as micromass cultures or as single cells within alginate gels, which were cultured in serum-free medium. Under these three-dimensional conditions, chondrogenesis is known to be supported and maintained. Cell cultures were exposed either to bone morphogenetic protein-2 (BMP-2) or to isoforms of transforming growth factor-β (TGF-β). The levels of mRNA for Sox9, collagen types I and II and aggrecan were determined by RT-PCR. Results: When transferred to alginate gel cultures, the fibroblast-like synovial cells assumed a rounded form. BMP-2, but not isoforms of TGF-β, stimulated, in a dose-dependent manner, the production of messenger RNAs (mRNAs) for Sox9, type II collagen and aggrecan. Under optimal conditions, the expression levels of cartilage-specific genes were comparable to those within cultured articular cartilage chondrocytes. However, in contrast to cultured articular cartilage chondrocytes, synovial cells exposed to BMP-2 continued to express the mRNA for α1(I) collagen. Conclusions: This study demonstrates that bovine synovium-derived mesenchymal progenitor cells can be induced to express chondrocyte-specific genes. However, the differentiation process is not complete under the chosen conditions. The stimulation conditions required for full transformation must now be delineated.
KW - BMP-2
KW - Chondrogenesis
KW - Differentiation
KW - Synoviocytes
UR - http://www.scopus.com/inward/record.url?scp=19144366775&partnerID=8YFLogxK
U2 - 10.1016/j.joca.2005.02.006
DO - 10.1016/j.joca.2005.02.006
M3 - Article
C2 - 15922187
AN - SCOPUS:19144366775
SN - 1063-4584
VL - 13
SP - 527
EP - 536
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 6
ER -