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Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase

Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are affected by inflammatory cytokines and pathological conditions. OPN is highly expressed in bone lesions such as those in rheumatoid arthritis. However, local regulatory effects of OPN on osteoblasts remain ambiguous. Here we...

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Autores principales: Kusuyama, Joji, Bandow, Kenjiro, Ohnishi, Tomokazu, Hisadome, Mitsuhiro, Shima, Kaori, Semba, Ichiro, Matsuguchi, Tetsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426847/
https://www.ncbi.nlm.nih.gov/pubmed/28331074
http://dx.doi.org/10.1091/mbc.E16-10-0716
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author Kusuyama, Joji
Bandow, Kenjiro
Ohnishi, Tomokazu
Hisadome, Mitsuhiro
Shima, Kaori
Semba, Ichiro
Matsuguchi, Tetsuya
author_facet Kusuyama, Joji
Bandow, Kenjiro
Ohnishi, Tomokazu
Hisadome, Mitsuhiro
Shima, Kaori
Semba, Ichiro
Matsuguchi, Tetsuya
author_sort Kusuyama, Joji
collection PubMed
description Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are affected by inflammatory cytokines and pathological conditions. OPN is highly expressed in bone lesions such as those in rheumatoid arthritis. However, local regulatory effects of OPN on osteoblasts remain ambiguous. Here we examined how OPN influences osteoblast responses to mechanical stress and growth factors. Expression of NO synthase 1 (Nos1) and Nos2 was increased by low-intensity pulsed ultrasound (LIPUS) in MC3T3-E1 cells and primary osteoblasts. The increase of Nos1/2 expression was abrogated by both exogenous OPN overexpression and recombinant OPN treatment, whereas it was promoted by OPN-specific siRNA and OPN antibody. Moreover, LIPUS-induced phosphorylation of focal adhesion kinase (FAK), a crucial regulator of mechanoresponses, was down-regulated by OPN treatments. OPN also attenuated hepatocyte growth factor–induced vitamin D receptor (Vdr) expression and platelet-derived growth factor–induced cell mobility through the repression of FAK activity. Of note, the expression of low–molecular weight protein tyrosine phosphatase (LMW-PTP), a FAK phosphatase, was increased in both OPN-treated and differentiated osteoblasts. CD44 was a specific OPN receptor for LWW-PTP induction. Consistently, the suppressive influence of OPN on osteoblast responsiveness was abrogated by LMW-PTP knockdown. Taken together, these results reveal novel functions of OPN in osteoblast physiology.
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spelling pubmed-54268472017-07-30 Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase Kusuyama, Joji Bandow, Kenjiro Ohnishi, Tomokazu Hisadome, Mitsuhiro Shima, Kaori Semba, Ichiro Matsuguchi, Tetsuya Mol Biol Cell Articles Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are affected by inflammatory cytokines and pathological conditions. OPN is highly expressed in bone lesions such as those in rheumatoid arthritis. However, local regulatory effects of OPN on osteoblasts remain ambiguous. Here we examined how OPN influences osteoblast responses to mechanical stress and growth factors. Expression of NO synthase 1 (Nos1) and Nos2 was increased by low-intensity pulsed ultrasound (LIPUS) in MC3T3-E1 cells and primary osteoblasts. The increase of Nos1/2 expression was abrogated by both exogenous OPN overexpression and recombinant OPN treatment, whereas it was promoted by OPN-specific siRNA and OPN antibody. Moreover, LIPUS-induced phosphorylation of focal adhesion kinase (FAK), a crucial regulator of mechanoresponses, was down-regulated by OPN treatments. OPN also attenuated hepatocyte growth factor–induced vitamin D receptor (Vdr) expression and platelet-derived growth factor–induced cell mobility through the repression of FAK activity. Of note, the expression of low–molecular weight protein tyrosine phosphatase (LMW-PTP), a FAK phosphatase, was increased in both OPN-treated and differentiated osteoblasts. CD44 was a specific OPN receptor for LWW-PTP induction. Consistently, the suppressive influence of OPN on osteoblast responsiveness was abrogated by LMW-PTP knockdown. Taken together, these results reveal novel functions of OPN in osteoblast physiology. The American Society for Cell Biology 2017-05-15 /pmc/articles/PMC5426847/ /pubmed/28331074 http://dx.doi.org/10.1091/mbc.E16-10-0716 Text en © 2017 Kusuyama et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Kusuyama, Joji
Bandow, Kenjiro
Ohnishi, Tomokazu
Hisadome, Mitsuhiro
Shima, Kaori
Semba, Ichiro
Matsuguchi, Tetsuya
Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase
title Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase
title_full Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase
title_fullStr Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase
title_full_unstemmed Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase
title_short Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase
title_sort osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low–molecular weight protein tyrosine phosphatase
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426847/
https://www.ncbi.nlm.nih.gov/pubmed/28331074
http://dx.doi.org/10.1091/mbc.E16-10-0716
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