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Bifunctional Role of CrkL during Bone Remodeling

Coupled signaling between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial to the maintenance of bone homeostasis. We previously reported that v-crk avian sarcoma virus CT10 oncogene homolog-like (CrkL), which belongs to the Crk family of adaptors, inhibits bone morphogenetic prote...

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Autores principales: Kim, Jung Ha, Kim, Kabsun, Kim, Inyoung, Seong, Semun, Kook, Hyun, Kim, Kyung Keun, Koh, Jeong-Tae, Kim, Nacksung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269069/
https://www.ncbi.nlm.nih.gov/pubmed/34209812
http://dx.doi.org/10.3390/ijms22137007
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author Kim, Jung Ha
Kim, Kabsun
Kim, Inyoung
Seong, Semun
Kook, Hyun
Kim, Kyung Keun
Koh, Jeong-Tae
Kim, Nacksung
author_facet Kim, Jung Ha
Kim, Kabsun
Kim, Inyoung
Seong, Semun
Kook, Hyun
Kim, Kyung Keun
Koh, Jeong-Tae
Kim, Nacksung
author_sort Kim, Jung Ha
collection PubMed
description Coupled signaling between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial to the maintenance of bone homeostasis. We previously reported that v-crk avian sarcoma virus CT10 oncogene homolog-like (CrkL), which belongs to the Crk family of adaptors, inhibits bone morphogenetic protein 2 (BMP2)-mediated osteoblast differentiation, while enhancing receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated whether CrkL can also regulate the coupling signals between osteoblasts and osteoclasts, facilitating bone homeostasis. Osteoblastic CrkL strongly decreased RANKL expression through its inhibition of runt-related transcription factor 2 (Runx2) transcription. Reduction in RANKL expression by CrkL in osteoblasts resulted in the inhibition of not only osteoblast-dependent osteoclast differentiation but also osteoclast-dependent osteoblast differentiation, suggesting that CrkL participates in the coupling signals between osteoblasts and osteoclasts via its regulation of RANKL expression. Therefore, CrkL bifunctionally regulates osteoclast differentiation through both a direct and indirect mechanism while it inhibits osteoblast differentiation through its blockade of both BMP2 and RANKL reverse signaling pathways. Collectively, these data suggest that CrkL is involved in bone homeostasis, where it helps to regulate the complex interactions of the osteoblasts, osteoclasts, and their coupling signals.
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spelling pubmed-82690692021-07-10 Bifunctional Role of CrkL during Bone Remodeling Kim, Jung Ha Kim, Kabsun Kim, Inyoung Seong, Semun Kook, Hyun Kim, Kyung Keun Koh, Jeong-Tae Kim, Nacksung Int J Mol Sci Article Coupled signaling between bone-forming osteoblasts and bone-resorbing osteoclasts is crucial to the maintenance of bone homeostasis. We previously reported that v-crk avian sarcoma virus CT10 oncogene homolog-like (CrkL), which belongs to the Crk family of adaptors, inhibits bone morphogenetic protein 2 (BMP2)-mediated osteoblast differentiation, while enhancing receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated whether CrkL can also regulate the coupling signals between osteoblasts and osteoclasts, facilitating bone homeostasis. Osteoblastic CrkL strongly decreased RANKL expression through its inhibition of runt-related transcription factor 2 (Runx2) transcription. Reduction in RANKL expression by CrkL in osteoblasts resulted in the inhibition of not only osteoblast-dependent osteoclast differentiation but also osteoclast-dependent osteoblast differentiation, suggesting that CrkL participates in the coupling signals between osteoblasts and osteoclasts via its regulation of RANKL expression. Therefore, CrkL bifunctionally regulates osteoclast differentiation through both a direct and indirect mechanism while it inhibits osteoblast differentiation through its blockade of both BMP2 and RANKL reverse signaling pathways. Collectively, these data suggest that CrkL is involved in bone homeostasis, where it helps to regulate the complex interactions of the osteoblasts, osteoclasts, and their coupling signals. MDPI 2021-06-29 /pmc/articles/PMC8269069/ /pubmed/34209812 http://dx.doi.org/10.3390/ijms22137007 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Jung Ha
Kim, Kabsun
Kim, Inyoung
Seong, Semun
Kook, Hyun
Kim, Kyung Keun
Koh, Jeong-Tae
Kim, Nacksung
Bifunctional Role of CrkL during Bone Remodeling
title Bifunctional Role of CrkL during Bone Remodeling
title_full Bifunctional Role of CrkL during Bone Remodeling
title_fullStr Bifunctional Role of CrkL during Bone Remodeling
title_full_unstemmed Bifunctional Role of CrkL during Bone Remodeling
title_short Bifunctional Role of CrkL during Bone Remodeling
title_sort bifunctional role of crkl during bone remodeling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269069/
https://www.ncbi.nlm.nih.gov/pubmed/34209812
http://dx.doi.org/10.3390/ijms22137007
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