Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing

Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing

Abstract Ultrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation...

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Autores principales: Tatsuya Shimizu, Naomasa Fujita, Kiyomi Tsuji-Tamura, Yoshimasa Kitagawa, Toshiaki Fujisawa, Masato Tamura, Mari Sato
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/156e0053c35f484fa3811aeab430d075
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spelling oai:doaj.org-article:156e0053c35f484fa3811aeab430d0752021-12-02T17:15:24ZOsteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing10.1038/s41598-021-89672-92045-2322https://doaj.org/article/156e0053c35f484fa3811aeab430d0752021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89672-9https://doaj.org/toc/2045-2322Abstract Ultrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation and how they contribute to fracture healing. To examine this, we utilized medaka, whose bone lacks osteocytes, and zebrafish, whose bone has osteocytes, as in vivo models. Fracture healing was accelerated by ultrasound stimulation in zebrafish, but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocytes, we performed RNA sequencing of a murine osteocytic cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation, and functional cluster analysis identified among them several molecular signatures related to immunity, secretion, and transcription. Notably, most of the isolated transcription-related genes were also modulated by LIPUS in vivo in zebrafish. However, expression levels of early growth response protein 1 and 2 (Egr1, 2), JunB, forkhead box Q1 (FoxQ1), and nuclear factor of activated T cells c1 (NFATc1) were not altered by LIPUS in medaka, suggesting that these genes are key transcriptional regulators of LIPUS-dependent fracture healing via osteocytes. We therefore show that bone-embedded osteocytes are necessary for LIPUS-induced promotion of fracture healing via transcriptional control of target genes, which presumably activates neighboring cells involved in fracture healing processes.Tatsuya ShimizuNaomasa FujitaKiyomi Tsuji-TamuraYoshimasa KitagawaToshiaki FujisawaMasato TamuraMari SatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tatsuya Shimizu
Naomasa Fujita
Kiyomi Tsuji-Tamura
Yoshimasa Kitagawa
Toshiaki Fujisawa
Masato Tamura
Mari Sato
Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
description Abstract Ultrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation and how they contribute to fracture healing. To examine this, we utilized medaka, whose bone lacks osteocytes, and zebrafish, whose bone has osteocytes, as in vivo models. Fracture healing was accelerated by ultrasound stimulation in zebrafish, but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocytes, we performed RNA sequencing of a murine osteocytic cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation, and functional cluster analysis identified among them several molecular signatures related to immunity, secretion, and transcription. Notably, most of the isolated transcription-related genes were also modulated by LIPUS in vivo in zebrafish. However, expression levels of early growth response protein 1 and 2 (Egr1, 2), JunB, forkhead box Q1 (FoxQ1), and nuclear factor of activated T cells c1 (NFATc1) were not altered by LIPUS in medaka, suggesting that these genes are key transcriptional regulators of LIPUS-dependent fracture healing via osteocytes. We therefore show that bone-embedded osteocytes are necessary for LIPUS-induced promotion of fracture healing via transcriptional control of target genes, which presumably activates neighboring cells involved in fracture healing processes.
format article
author Tatsuya Shimizu
Naomasa Fujita
Kiyomi Tsuji-Tamura
Yoshimasa Kitagawa
Toshiaki Fujisawa
Masato Tamura
Mari Sato
author_facet Tatsuya Shimizu
Naomasa Fujita
Kiyomi Tsuji-Tamura
Yoshimasa Kitagawa
Toshiaki Fujisawa
Masato Tamura
Mari Sato
author_sort Tatsuya Shimizu
title Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
title_short Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
title_full Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
title_fullStr Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
title_full_unstemmed Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
title_sort osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/156e0053c35f484fa3811aeab430d075
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AT naomasafujita osteocytesasmainresponderstolowintensitypulsedultrasoundtreatmentduringfracturehealing
AT kiyomitsujitamura osteocytesasmainresponderstolowintensitypulsedultrasoundtreatmentduringfracturehealing
AT yoshimasakitagawa osteocytesasmainresponderstolowintensitypulsedultrasoundtreatmentduringfracturehealing
AT toshiakifujisawa osteocytesasmainresponderstolowintensitypulsedultrasoundtreatmentduringfracturehealing
AT masatotamura osteocytesasmainresponderstolowintensitypulsedultrasoundtreatmentduringfracturehealing
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