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Title: Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts

Abstract

Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules. - Highlights: • Tspan7 expression is up-regulated during osteoclastogenesis. • Tspan7 regulates podosome belt organization in osteoclasts. • Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts. • Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.

Authors:
; ; ; ; ; ;
Publication Date:
OSTI Identifier:
22606200
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 477; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLATION; DENTIN; GENES; MICROTUBULES; MORPHOLOGY; PHOSPHORYLATION; PROTEINS; SKELETON

Citation Formats

Kwon, Jun-Oh, Lee, Yong Deok, Kim, Haemin, Kim, Min Kyung, Song, Min-Kyoung, Lee, Zang Hee, and Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr. Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.07.046.
Kwon, Jun-Oh, Lee, Yong Deok, Kim, Haemin, Kim, Min Kyung, Song, Min-Kyoung, Lee, Zang Hee, & Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr. Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts. United States. doi:10.1016/J.BBRC.2016.07.046.
Kwon, Jun-Oh, Lee, Yong Deok, Kim, Haemin, Kim, Min Kyung, Song, Min-Kyoung, Lee, Zang Hee, and Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr. 2016. "Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts". United States. doi:10.1016/J.BBRC.2016.07.046.
@article{osti_22606200,
title = {Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts},
author = {Kwon, Jun-Oh and Lee, Yong Deok and Kim, Haemin and Kim, Min Kyung and Song, Min-Kyoung and Lee, Zang Hee and Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr},
abstractNote = {Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules. - Highlights: • Tspan7 expression is up-regulated during osteoclastogenesis. • Tspan7 regulates podosome belt organization in osteoclasts. • Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts. • Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.},
doi = {10.1016/J.BBRC.2016.07.046},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 477,
place = {United States},
year = 2016,
month = 9
}
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