title: Mechanisms underlying the synergistic enhancement of self-assembled neocartilage treated with chondroitinase-ABC and TGF-β1.
abstract: Developing a platform for in vitro cartilage formation would enhance the study of cartilage development, pathogenesis, and regeneration. To improve neocartilage formation, our group developed a novel self-assembly process for articular chondrocytes, which has been improved in this study using a novel combination of catabolic and anabolic agents. TGF-β1 was applied in conjunction with the enzyme chondroitinase-ABC (C-ABC) to additively increase tensile properties and synergistically enhance collagen content. Additionally, microarray analysis indicated that TGF-β1 up-regulated MAPK signaling in contrast to C-ABC, which did not enrich genetic pathways. The lack of genetic signaling spurred investigation of the biophysical role of C-ABC, which showed that C-ABC treatment increased collagen fibril diameter and density. After four weeks of culture in nude mice, neocartilage exhibited stability and maturation. This study illustrated an innovative strategy for improving in vitro and in vivo articular cartilage formation and elucidated mechanisms underlying TGF-β1 and C-ABC treatment.
authors.affiliation: Department of Biomedical Engineering, University of California Davis, One Shields Ave, Davis, CA 95616, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Responte
authors.forename: Boaz
authors.initials: B
authors.lastname: Arzi
authors.forename: Roman M
authors.initials: RM
authors.lastname: Natoli
authors.forename: Jerry C
authors.initials: JC
authors.lastname: Hu
authors.forename: Kyriacos A
authors.initials: KA
authors.lastname: Athanasiou
mesh_terms: D000818:Animals; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D019765:Chondroitin ABC Lyase / Q000494:pharmacology*; D008422:Materials Testing; D023822:Tissue Engineering / Q000295:instrumentation*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1; D019765:Chondroitin ABC Lyase