2015
DOI: 10.1074/jbc.m115.641670
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Lysyl Oxidase Activity Is Required for Ordered Collagen Fibrillogenesis by Tendon Cells

Abstract: Background: Lysyl oxidase catalyzes collagen cross-link formation, which is essential for mechanically strong collagen fibrils. Results: LOX inhibition stops early mechanical development of tendon constructs and leads to irregularly shaped collagen fibrils. Conclusion: Collagen cross-linking is essential for successful fibrillogenesis and regulates fibril shape. Significance: LOX activity is required in the control of collagen fibril architecture by a mechanism that remains to be explained.

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Cited by 144 publications
(102 citation statements)
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“…The sequential ionic and covalent crosslinking of aECM here is analogous to how collagen is covalently modified in tissues. Following collagen self-assembly, enzymatic crosslinking by lysyl oxidase further crosslinks assembled collagen fibers [26, 36, 37] to alter their mechanical properties without altering the overall ECM content of the tissue [38]. Together, these studies demonstrate one approach to build complex hierarchical structures of extracellular matrix with tunable mechanical properties.…”
Section: Discussionmentioning
confidence: 99%
“…The sequential ionic and covalent crosslinking of aECM here is analogous to how collagen is covalently modified in tissues. Following collagen self-assembly, enzymatic crosslinking by lysyl oxidase further crosslinks assembled collagen fibers [26, 36, 37] to alter their mechanical properties without altering the overall ECM content of the tissue [38]. Together, these studies demonstrate one approach to build complex hierarchical structures of extracellular matrix with tunable mechanical properties.…”
Section: Discussionmentioning
confidence: 99%
“…After 24 h, total RNA was extracted using TRIzol reagent (Invitrogen), and 1 μ g of RNA was converted into cDNA using the ImProm‐II Reverse Transcription System (Promega, Madison, WI, USA). Quantitative real‐time PCR procedures were performed using LightCycler 480 SYBR Green I Master (Roche Diagnostics, Mannheim, Germany), an equal amount of cDNA, and specific primers for genes encoding type I collagen and its modifying enzymes, as follows: collagen type I alpha‐2 chain ( COL1A2 ) , 5′‐TAATGGGGAAGCTGGATCTG‐3′ (forward) and 5′‐GTCCCTGAGCACCATTGTTT‐3′ (reverse); LH1 ( PLOD1 ) , 5′‐GAAGCTCTACCCCGGCTACT‐3′ (forward) and 5′‐CTTGTAGCGGACGACAAAGG‐3′ (reverse); LH2 ( PLOD2 ) , 5′‐GGGAGTTCATTGCACCAGTT‐3′ (forward) and 5′‐GAGGACGAAGAGAACGCTGT‐3′ (reverse); LH3: PLOD3 , 5′‐CACTACGGCCAGTGGTCAG‐3′ (forward) and 5′‐GTGGGCACATTCTCGTAGC‐3′ (reverse); GLT25D1 ( GLT25D1 ) , 5′‐GATGCTGCCTGTGGACGAGTTC‐3′ (forward) and 5′‐CTCACATAGCCATCGTCTCCTG‐3′ (reverse); LOX ( LOX ) , 5′‐CGCTGTGACATTCGCTACACAGGAC‐3′ (forward) and 5′‐CATTGGGAGTTTTGCTTTGCCTTCT‐3′ (reverse); and glyceraldehyde‐3‐phosphate dehydrogenase ( GAPDH ) , 5′‐GCTCTCCAGAACATCATCC‐3′ (forward) and 5′‐GTGTCGCTGTTGAAGTCAG‐3′ (reverse). Results were analyzed using the LightCycler 480 Instrument (Roche Diagnostics).…”
Section: Methodsmentioning
confidence: 99%
“…42 It was beyond the scope of the present study to measure these factors. Clearly, tendon mechanical properties can be influenced by other factors than the fibril structures, and enzymatic as well as non-enzymatic cross-links have been shown to influence tendon stiffness.…”
mentioning
confidence: 96%