Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale

Kobayashi-Sun, Jingjing; Yamamori, Shiori; Kondo, Mao; Kuroda, Junpei; Ikegame, Mika; Suzuki, Nobuo; Kitamura, Kei; Hattori, Atsuhiko; Yamaguchi, Masatoshi; Kobayashi, Isao

doi:10.1038/s42003-020-0925-1

Cited by 56 publications

(60 citation statements)

References 54 publications

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“…In an alternative scenario, our observation of upregulated osteogenic transcripts in osteoclasts could reflect the uptake of osteoblast-released exosomes, a process that was recently shown to occur in regenerating zebrafish scales. (64) These osteoblast-derived exosomes could not only contain factors driving osteoclast differentiation, as reported by Kobayashi-Sun and colleagues, (64) but also osteogenic mRNAs. However, we observed that the majority of upregulated osteogenic genes (i) is already expressed at basal levels in noninduced macrophages, and (ii) encode secreted or transmembrane proteins.…”

Section: Dynamic Transcriptome Changes In Activated Macrophages Suggementioning

confidence: 63%

Macrophages Switch to an Osteo‐Modulatory Profile Upon RANKL Induction in a Medaka (Oryzias latipes) Osteoporosis Model

et al. 2020

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In mammals, osteoclasts differentiate from macrophages in the monocyte lineage. Although many factors driving osteoclast formation are known, the detailed processes underlying precursor recruitment, differentiation, and interaction of macrophages with other cell types involved in bone remodeling are poorly understood. Using live imaging in a transgenic medaka osteoporosis model, where ectopic osteoclasts are induced by RANKL expression, we show that a subset of macrophages is recruited to bone matrix to physically interact with bone-forming osteoblast progenitors. These macrophages subsequently differentiate into cathepsin K-(ctsk-) positive osteoclasts. One day later, other macrophages are recruited to clear dying osteoclasts from resorbed bone by phagocytosis. To better understand the molecular changes underlying these dynamic processes, we performed transcriptome profiling of activated macrophages upon RANKL induction. This revealed an upregulation of several bone-related transcripts. Besides osteoclast markers, we unexpectedly also found expression of osteoblast-promoting signals in activated macrophages, suggesting a possible non-cell autonomous role in osteogenesis. Finally, we show that macrophage differentiation into osteoclasts is dependent on inflammatory signals. Medaka deficient for TNFα or treated with the TNFα-inhibitor pentoxifylline exhibited impaired macrophage recruitment and osteoclast differentiation. These results show the involvement of inflammatory signals and the dynamics of a distinct subset of macrophages during osteoclast formation.

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Section: Dynamic Transcriptome Changes In Activated Macrophages Suggementioning

confidence: 63%

Macrophages Switch to an Osteo‐Modulatory Profile Upon RANKL Induction in a Medaka (Oryzias latipes) Osteoporosis Model

et al. 2020

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“…Fractured zebrafish scales revealed a previously unrecognized cellular mechanism of osteoblast–osteoclast communication via osteoblast‐derived extracellular vesicles promoting osteoclast differentiation. ( 255 )…”

Section: Modeling Hormonal Bone Disorders In Zebrafish Fins and Scalesmentioning

confidence: 99%

Skeletal Biology and Disease Modeling in Zebrafish

Dietrich

Fiedler

Kurzyukova

et al. 2020

Journal of Bone and Mineral Research

104

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Zebrafish are teleosts (bony fish) that share with mammals a common ancestor belonging to the phylum Osteichthyes, from which their endoskeletal systems have been inherited. Indeed, teleosts and mammals have numerous genetically conserved features in terms of skeletal elements, ossification mechanisms, and bone matrix components in common. Yet differences related to bone morphology and function need to be considered when investigating zebrafish in skeletal research. In this review, we focus on zebrafish skeletal architecture with emphasis on the morphology of the vertebral column and associated anatomical structures. We provide an overview of the different ossification types and osseous cells in zebrafish and describe bone matrix composition at the microscopic tissue level with a focus on assessing mineralization. Processes of bone formation also strongly depend on loading in zebrafish, as we elaborate here. Furthermore, we illustrate the high regenerative capacity of zebrafish bones and present some of the technological advantages of using zebrafish as a model. We highlight zebrafish axial and fin skeleton patterning mechanisms, metabolic bone disease such as after immunosuppressive glucocorticoid treatment, as well as osteogenesis imperfecta (OI) and osteopetrosis research in zebrafish. We conclude with a view of why larval zebrafish xenografts are a powerful tool to study bone metastasis. © 2021 American Society for Bone and Mineral Research (ASBMR).

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“…In a similar fashion, Deng et al have shown the benefit of inhibiting the release of receptor activator of nuclear factor kappa-Β ligand (RANK-L)-positive EVs from osteoblasts in ovariectomized mice as a method of significantly reducing bone loss [ 78 ]. While the ovariectomized mouse does not represent a model of autoimmunity, the activity of RANK-L-positive EVs in the formation of mature, multi-nucleated osteoclasts, and indeed exaggerated bone loss, remains relevant to the study of RA [ 79 , 80 ].…”

Section: The Role Of Ev Cargo In Modulating Cytokine Production Dumentioning

confidence: 99%

The Role and Impact of Extracellular Vesicles in the Modulation and Delivery of Cytokines during Autoimmunity

Hussain

Iqbal

Norling

2020

IJMS

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Cytokines and extracellular vesicles are two methods of initiating and maintaining cellular crosstalk. The role of cytokines in the initiation, progression, and resolution of inflammation has been well studied and more so, their pathophysiological role in the development of autoimmune disease. In recent years, the impact of extracellular vesicles on the progression of autoimmunity has become more widely appreciated. In this review, we discuss the mechanisms that allow extracellular vesicles of various sources to modulate cytokine production, and release, and how extracellular vesicles might be involved in the direct delivery and modulation of cytokine levels. Moreover, we explore what challenges are faced by current therapies and the promising future for extracellular vesicles as therapeutic agents in conditions driven by immune dysregulation.

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Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale

Cited by 56 publications

References 54 publications

Macrophages Switch to an Osteo‐Modulatory Profile Upon RANKL Induction in a Medaka (Oryzias latipes) Osteoporosis Model

Macrophages Switch to an Osteo‐Modulatory Profile Upon RANKL Induction in a Medaka (Oryzias latipes) Osteoporosis Model

Skeletal Biology and Disease Modeling in Zebrafish

The Role and Impact of Extracellular Vesicles in the Modulation and Delivery of Cytokines during Autoimmunity

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