title: Matrix dimensions, stiffness, and structural properties modulate spontaneous chondrogenic commitment of mouse embryonic fibroblasts.
abstract: 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 (∼ 0.1 kPa). Interestingly, under these conditions, the system expressed the chondrogenic inductor BMP4 and its antagonist Noggin. On the other hand, at higher elastic modulus values (∼ 5 kPa), 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.
authors: 1 Tissue Engineering Laboratory , Department of Bioengineering, IQS School of Engineering, Barcelona, Spain .
authors: Teresa
authors: T
authors: Fernández-Muiños
authors: Melva
authors: M
authors: Suárez-Muñoz
authors: Marta
authors: M
authors: Sanmartí-Espinal
authors: Carlos E
authors: CE
authors: Semino
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002356:Cartilage / Q000166:cytology / Q000502:physiology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D020219:Chondrogenesis; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000166:cytology*; D005109:Extracellular Matrix / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006025:Glycosaminoglycans / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D010012:Osteogenesis; D054457:Tissue Scaffolds / Q000737:chemistry; D015854:Up-Regulation; D000099176:Noggin Protein
chemical_list: D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D006025:Glycosaminoglycans; D000099176:Noggin Protein