Hypoxia-induced collagen crosslinking as a mechanism for enhancing mechanical properties of engineered articular cartilage
Ημερομηνία
2013Λέξη-κλειδί
Επιτομή
Objective: The focus of tissue engineering of neocartilage has traditionally been on enhancing extracellular matrix and thus biomechanical properties. Emphasis has been placed on the enhancement of collagen type and quantity, and, concomitantly, tensile properties. The objective of this study was to improve crosslinking of the collagen network by testing the hypothesis that hypoxia could promote pyridinoline (PYR) crosslinks and, thus, improve neocartilage's tensile properties. Methods: Chondrocyte expression of lysyl oxidase (LOX), an enzyme responsible for the formation of collagen PYR crosslinks, was first assessed pre- and post- hypoxia application. Then, the mechanical properties of self-assembled neocartilage constructs were measured, after 4 weeks of culture, for groups exposed to 4% O2 at different initiation times and durations, i.e., during the 1st and 3rd weeks, 3rd and 4th weeks, 4th week only, continuously after cell seeding, or never. Results: Results showed that LOX gene expression was upregulated ∼20-fold in chondrocytes in response to hypoxia. Hypoxia applied during the 3rd and 4th weeks significantly increased PYR crosslinks without affecting collagen content. Excitingly, neocartilage tensile properties were increased ∼2-fold. It should be noted that these properties exhibited a distinct temporal dependence to hypoxia exposure, since upregulation of these properties was due to hypoxia applied only during the 3rd and 4th weeks. Conclusion: These data elucidate the role of hypoxia-mediated upregulation of LOX and subsequent increases in PYR crosslinks in engineered cartilage. These results hold promise toward applying hypoxia at precise time points to promote tensile integrity and direct construct maturation. © 2013 Osteoarthritis Research Society International.
Collections
Related items
Showing items related by title, author, creator and subject.
-
Differential expression of leptin and leptin's receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism
Simopoulou, T.; Malizos, K. N.; Iliopoulos, D.; Stefanou, N.; Papatheodorou, L.; Ioannou, M.; Tsezou, A. (2007)Objective: To investigate leptin's effect on cartilage metabolism and the pathophysiology of osteoarthritis (OA). Methods: Messenger RNA (mRNA) expression and protein levels of leptin and leptin's receptor isoforms were ... -
Induced Collagen Cross-Links Enhance Cartilage Integration
Athens, A. A.; Makris, E. A.; Hu, J. C. (2013)Articular cartilage does not integrate due primarily to a scarcity of cross-links and viable cells at the interface. The objective of this study was to test the hypothesis that lysyl-oxidase, a metalloenzyme that forms ... -
COMP serum levels: A new non-invasive biomarker of liver fibrosis in patients with chronic viral hepatitis
Zachou K., Gabeta S., Shums Z., Gatselis N.K., Koukoulis G.K., Norman G.L., Dalekos G.N. (2017)Background & aims Recently we have shown that cartilage oligomeric matrix protein (COMP), a fibrillar collagen assembly regulator, is strongly associated with cirrhosis and hepatocellular carcinoma progression. Therefore, ...