The integrin α5β1 regulates chondrocyte hypertrophic differentiation induced by GTP-bound transglutaminase 2
Use this link to cite this item : https://ir.lib.hiroshima-u.ac.jp/00020636
ID | 20636 |
file | |
creator |
Tanaka, Kumi
Higashikawa, Fumiko
Saito, Yuji
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subject | Integrin
Transglutaminase 2
Chondrocyte
Hypertrophy
Differentiation
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NDC |
Biology
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abstract | Soluble GTP-bound transglutaminase 2 (TG2) induces hypertrophic differentiation in chondrocyte cultures in a β1 integrin-dependent fashion. β1 integrin subfamily consists of 12 heterodimers with 12 different α subunits and a β1 subunit. To identify the specific integrin heterodimer(s) responsible for this process, we specifically blocked individual β1 integrins on the CH-8 immortalized human chondrocytes during hypertrophic differentiation. Blockade of α5β1 inhibited matrix metalloproteinase 13 (MMP-13), type X collagen expression, alkaline phosphatase activity, and matrix calcification by 30-50 %, associated with weak effects of anti-α3β1 and -α4β1. Anti-α1β1, -α2β1 and -α6β1 had no effect. To examine whether the dominant effect of integrin α5β1 was due to a direct interaction with TG2, we incubated the chondrocytic cells on plates coated with GTP-bound TG2. The immobilized GTP-bound TG2 induced hypertrophic differentiation to the same extent as the soluble GTP-bound TG2, which was also inhibited by anti-α5β1. CH-8 cells grown on plates coated with GTP-bound TG2 demonstrated adherence associated with focal adhesion kinase phosphorylation. These properties were inhibited by anti-α5β1. Furthermore, engagement of α5β1 on CH-8 cells via anti-α5β1 antibody did, in fact, induce differentiation. Although CH-8 cells adhered to GTP-free TG2 via integrin α5β1, the cells failed to undergo hypertrophic differentiation. Thus, integrin α5β1 is critical for the chondrocyte hypertrophic differentiation induced by GTP-bound TG2, and this induction is ligand-dependent.
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journal title |
Matrix Biology
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volume | Volume 26
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issue | Issue 2
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start page | 409
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end page | 418
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date of issued | 2007-06
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publisher | Elsevier B.V.
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issn | 0945-053X
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ncid | |
publisher doi | |
language |
eng
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nii type |
Journal Article
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HU type |
Journal Articles
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DCMI type | text
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format | application/pdf
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text version | author
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rights | Copyright (c) 2007 International Society of Matrix Biology Published by Elsevier B.V.
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relation url | |
department |
Health Service Center
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