TY - JOUR
T1 - Matrix dimensions, stiffness, and structural properties modulate spontaneous chondrogenic commitment of mouse embryonic fibroblasts
AU - Fernández-Muiños, Teresa
AU - Suárez-Muñoz, Melva
AU - Sanmartí-Espinal, Marta
AU - Semino, Carlos E.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Experimental models for cartilage and bone development have been studied in order to understand the biomechanical and biological parameters that regulate skeletal tissue formation. We have previously described that when mouse embryonic fibroblasts (MEFs) were cultured in a three-dimensional (3D)-soft self-assembling peptide nanofiber, the system engaged in a spontaneous process of cartilage-like formation evidenced by the expression of Sox9, Collagen type II, and proteoglycans. In the present work, we studied the influence that matrix mechanical properties have in modulating lineage commitment in an in vitro model of chondrogenesis. This effect was observed only when MEFs were cultured at low elastic modulus values (∼0.1kPa). Interestingly, under these conditions, the system expressed the chondrogenic inductor BMP4 and its antagonist Noggin. On the other hand, at higher elastic modulus values (∼5kPa), the system expressed Noggin but not BMP4, and did not engage in chondrogenesis, which suggest that the balance between bone morphogenetic protein/Noggin could be implicated in the chondrogenic process. Finally, no evidence of hypertrophy was detected under the conditions tested (by assessing expression of Collagen type X and Runx2) unless we challenged the system by co-culturing it with endothelial cells. Importantly, under these new conditions, the system underwent spontaneous matrix calcium mineralization. These results suggest that the 3D-system described here is sensitive to respond to environmental changes such as biomechanical and biological cues.
AB - Experimental models for cartilage and bone development have been studied in order to understand the biomechanical and biological parameters that regulate skeletal tissue formation. We have previously described that when mouse embryonic fibroblasts (MEFs) were cultured in a three-dimensional (3D)-soft self-assembling peptide nanofiber, the system engaged in a spontaneous process of cartilage-like formation evidenced by the expression of Sox9, Collagen type II, and proteoglycans. In the present work, we studied the influence that matrix mechanical properties have in modulating lineage commitment in an in vitro model of chondrogenesis. This effect was observed only when MEFs were cultured at low elastic modulus values (∼0.1kPa). Interestingly, under these conditions, the system expressed the chondrogenic inductor BMP4 and its antagonist Noggin. On the other hand, at higher elastic modulus values (∼5kPa), the system expressed Noggin but not BMP4, and did not engage in chondrogenesis, which suggest that the balance between bone morphogenetic protein/Noggin could be implicated in the chondrogenic process. Finally, no evidence of hypertrophy was detected under the conditions tested (by assessing expression of Collagen type X and Runx2) unless we challenged the system by co-culturing it with endothelial cells. Importantly, under these new conditions, the system underwent spontaneous matrix calcium mineralization. These results suggest that the 3D-system described here is sensitive to respond to environmental changes such as biomechanical and biological cues.
KW - Mesenchymal stem-cells
KW - Endochondral ossification
KW - Osteogenic differentiation
KW - Bone
KW - Cartilage
KW - Noggin
KW - Sox9
KW - Proliferation
KW - Morphogenesis
KW - Paradigm
UR - http://www.scopus.com/inward/record.url?scp=84898634990&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000334110000004&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1089/ten.tea.2013.0369
DO - 10.1089/ten.tea.2013.0369
M3 - Article
C2 - 24329135
AN - SCOPUS:84898634990
SN - 1937-3341
VL - 20
SP - 1145
EP - 1155
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
IS - 7-8
ER -