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Erschienen in:

20.10.2020 | Invited Review

Osteoclast differentiation by RANKL and OPG signaling pathways

verfasst von: Nobuyuki Udagawa, Masanori Koide, Midori Nakamura, Yuko Nakamichi, Teruhito Yamashita, Shunsuke Uehara, Yasuhiro Kobayashi, Yuriko Furuya, Hisataka Yasuda, Chie Fukuda, Eisuke Tsuda

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 1/2021

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Abstract

Introduction

In bone tissue, bone resorption by osteoclasts and bone formation by osteoblasts are repeated continuously. Osteoclasts are multinucleated cells that derive from monocyte-/macrophage-lineage cells and resorb bone. In contrast, osteoblasts mediate osteoclastogenesis by expressing receptor activator of nuclear factor-kappa B ligand (RANKL), which is expressed as a membrane-associated cytokine. Osteoprotegerin (OPG) is a soluble RANKL decoy receptor that is predominantly produced by osteoblasts and which prevents osteoclast formation and osteoclastic bone resorption by inhibiting the RANKL–RANKL receptor interaction.

Materials and Methods

In this review, we would like to summarize our experimental results on signal transduction that regulates the expression of RANKL and OPG.

Results

Using OPG gene-deficient mice, we have demonstrated that OPG and sclerostin produced by osteocytes play an important role in the maintenance of cortical and alveolar bone. In addition, it was shown that osteoclast-derived leukemia inhibitory factor (LIF) reduces the expression of sclerostin in osteocytes and promotes bone formation. WP9QY (W9) is a peptide that was designed to be structurally similar to one of the cysteine-rich TNF-receptortype-I domains. Addition of the W9 peptide to bone marrow culture simultaneously inhibited osteoclast differentiation and stimulated osteoblastic cell proliferation. An anti-sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) antibody inhibited multinucleated osteoclast formation induced by RANKL and macrophage colony-stimulating factor (M-CSF). Pit-forming activity of osteoclasts was also inhibited by the anti-Siglec-15 antibody. In addition, anti-Siglec-15 antibody treatment stimulated the appearance of osteoblasts in cultures of mouse bone marrow cells in the presence of RANKL and M-CSF.

Conclusions

Bone mass loss depends on the RANK–RANKL–OPG system, which is a major regulatory system of osteoclast differentiation induction, activation, and survival.

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Titel: Osteoclast differentiation by RANKL and OPG signaling pathways
verfasst von: Nobuyuki Udagawa
Masanori Koide
Midori Nakamura
Yuko Nakamichi
Teruhito Yamashita
Shunsuke Uehara
Yasuhiro Kobayashi
Yuriko Furuya
Hisataka Yasuda
Chie Fukuda
Eisuke Tsuda
Publikationsdatum: 20.10.2020
Verlag: Springer Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 1/2021
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-020-01162-6

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Osteoclast differentiation by RANKL and OPG signaling pathways

Abstract

Introduction

Materials and Methods

Results

Conclusions

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