Hypoxia-induced collagen crosslinking as a mechanism for enhancing mechanical properties of engineered articular cartilage.
Hypoxia-induced collagen crosslinking as a mechanism for enhancing mechanical properties of engineered articular cartilage.
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DOI：
10.1016/j.joca.2013.01.007
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发表时间：
2013-04
影响因子：
7
通讯作者：
Athanasiou, K. A.
中科院分区：
文献类型：
--
作者：
Makris, E. A.;Hu, J. C.;Athanasiou, K. A.
关键词：
传统上，新软骨的组织工程的重点是增强细胞外基质，从而提高生物力学性能。重点放在胶原类型和数量的增强上，以及随之而来的拉伸性能。本研究的目的是通过测试缺氧可以促进吡啶啉（PYR）交联，从而改善新生软骨的拉伸性能的假设，以提高胶原网络的交联。首先在缺氧应用之前和之后评估赖氨酰氧化酶（LOX）（一种负责形成胶原PYR交联的酶）的软骨细胞表达。然后，在培养4周后，对于暴露于4%O2的组，在不同的起始时间和持续时间，即，在第1和第3周期间、第3和第4周期间、仅第4周、在细胞接种后连续地、或从不。结果表明，LOX基因的表达上调约20倍，在软骨细胞在缺氧反应。在第3周和第4周期间施加的低氧显著增加PYR交联而不影响胶原含量。令人兴奋的是，新软骨的拉伸性能增加了约2倍。应该注意的是，这些特性表现出对缺氧暴露的明显时间依赖性，因为这些特性的上调是由于仅在第3周和第4周期间施加的缺氧。这些数据阐明了低氧介导的LOX上调和随后的PYR交联在工程化软骨中的增加的作用。这些结果有希望在精确的时间点应用缺氧，以促进拉伸完整性和直接结构成熟。
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. 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 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. 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.
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影响因子：
7
作者：
Buckley, C. T.;Vinardell, T.;Kelly, D. J.
通讯作者：
Kelly, D. J.
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
4.1
作者：
Ahmed, MU;Frye, EB;Baynes, JW
通讯作者：
Baynes, JW
影响因子：
2.8
作者：
Das, R. H. J.;van Osch, G. J. V. M.;Jahr, H.
通讯作者：
Jahr, H.
影响因子：
4.1
作者：
Bank, RA;Bayliss, MT;Tekoppele, JM
通讯作者：
Tekoppele, JM