Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cho, Eunjin; Cheon, Seongmin; Ding, Mina; Lim, Kayeong; Park, Sang-Wook; Park, Chungoo; Lee, Tae‐Hoon

doi:10.3390/ijms23126421

Cited by 3 publications

(2 citation statements)

References 64 publications

(77 reference statements)

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“…During osteoclast development, BMMs initially differentiate into TRAP-positive monocyte with M-CSF and RANKL stimulation, which are also called preosteoclast, then the formed pre-osteoclasts migrate to bone surface and fuse with other pre-osteoclasts or formed osteoclasts to turn into functionally activated multinucleated osteoclast cells. As previously reported by the studies, blocking the migratory or fusion behaviors of pre-osteoclasts were also effective in reducing formation of mature thereby reducing pathologic bone loss in disease models [24][25][26]. Our study shows that the migration of preosteoclasts induced by M-CSF is inhibited in the presence of CL.…”

Section: Discussionsupporting

confidence: 87%

Attenuating bone loss in osteoporosis: the potential of corylin (CL) as a therapeutic agent

Zhou,

Huang,

Chen

et al. 2024

Aging

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Section: Discussionsupporting

confidence: 87%

Attenuating bone loss in osteoporosis: the potential of corylin (CL) as a therapeutic agent

Zhou,

Huang,

Chen

et al. 2024

Aging

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“…Cell fusion, a pervasive phenomenon in both physiological and pathological contexts, is essential for processes such as zygote formation [3], myogenesis [4], osteoclastogenesis [5], and wound healing [6]. The concept that tumor cells possess the ability to fuse with other cells has been postulated since 1911 [7].…”

Section: Introductionmentioning

confidence: 99%

Glioma Cells Achieve Malignant Progression by Fusion with Macrophages to Gain High SLC7A5 Expression

yuedong,

Li,

Liu

et al. 2024

Preprint

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Background Glioma is the most prevalent primary tumor of the central nervous system (CNS) in adults, and its high proliferative and invasive capacities are typically associated with a poor prognosis. Cell fusions are a crucial phenomenon in both physiological and pathological processes. Within tumors, tumor cells can acquire diverse gene expression profiles and undergo malignant progression through fusion events with themselves or other somatic cells. This process leads to the emergence of stem cell characteristics, drug resistance properties, immune evasion abilities, and enhanced migration and invasion capacities. Macrophages (MФs) represent the predominant cell type within glioma immune microenvironments and are important partners for fusion events with glioma cells. However, the biological characteristics and underlying mechanisms of MФ-glioma fusion hybrids remain incompletely elucidated. Results We validated the presence of MФ-glioma double positive cells through analysis of glioma single-cell RNA sequencing (scRNA-seq) data and examination of glioma specimens. We successfully established the MФ-glioma cell fusion hybrid models in vitro. Subsequent propidium iodide (PI) staining combined with flow cytometry analysis revealed a significant increase in the chromosome content of hybrid cells. Research on the biological characteristics of MФ-glioma fusion hybrids has revealed their heightened proliferation and invasion capabilities. Further mechanistic investigations have elucidated that SLC7A5, a tumor-associated gene originating from parental MФs, orchestrates the augmented proliferative and invasive capabilities of hybrid cells via activation of the mTOR-RPS6 signaling pathway. Furthermore, the MФ-glioma fusion hybrids exhibited heightened sensitivity to a specific inhibitor of SLC7A5 (JPH203) compared to their parental cells. Conclusion Glioma cells achieve malignant progression by acquiring high expression of the tumor-associated gene SLC7A5 through fusion with MФs. This discovery provides a new perspective on the malignant biology of gliomas.

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Myrislignan targets extracellular signal-regulated kinase (ERK) and modulates mitochondrial function to dampen osteoclastogenesis and ovariectomy-induced osteoporosis

Yang,

Chen,

Gan

et al. 2023

J Transl Med

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Background Activated osteoclasts cause excessive bone resorption, and disrupt bone homeostasis, leading to osteoporosis. The extracellular signal-regulated kinase (ERK) signaling is the classical pathway related to osteoclast differentiation, and mitochondrial reactive oxygen species are closely associated with the differentiation of osteoclasts. Myrislignan (MRL), a natural product derived from nutmeg, has multiple pharmacological activities; however, its therapeutic effect on osteoporosis is unclear. Here, we investigated whether MRL could inhibit osteoclastogenesis and bone mass loss in an ovariectomy mouse model by suppressing mitochondrial function and ERK signaling. Methods Tartrate-resistant and phosphatase (TRAP) and bone resorption assays were performed to observe the effect of MRL on osteoclastogenesis of bone marrow macrophages. MitoSOX RED and tetramethyl rhodamine methyl ester (TMRM) staining was performed to evaluate the inhibitory effect of MRL on mitochondria. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was performed to detect whether MRL suppressed the expression of osteoclast-specific genes. The impact of MRL on the protein involved in the mitogen-activated protein kinase (MAPK) and nuclear factor-κB pathways was evaluated using western blotting. In addition, a specific ERK agonist LM22B-10, was used to revalidate the inhibitory effect of MRL on ERK. Finally, we established an ovariectomy mouse model to assess the therapeutic effect of MRL on osteoporosis in vivo. Results MRL inhibited osteoclast differentiation and the associated bone resorption, by significantly decreasing osteoclastic gene expression. Mechanistically, MRL inhibited the phosphorylation of ERK by suppressing the mitochondrial function, thereby downregulating the nuclear factor of activated T cells 1 (NFATc1) signaling. LM22B-10 treatment further verified the targeted inhibition effect of MRL on ERK. Microscopic computed tomographic and histologic analyses of the tibial tissue sections indicated that ovariectomized mice had lower bone mass and higher expression of ERK compared with normal controls. However, MRL treatment significantly reversed these effects, indicating the anti-osteoporosis effect of MRL. Conclusion We report for the first time that MRL inhibits ERK signaling by suppressing mitochondrial function, thereby ameliorating ovariectomy-induced osteoporosis. Our findings can provide a basis for the development of a novel therapeutic strategy for osteoporosis.

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Identification of Novel Genes for Cell Fusion during Osteoclast Formation

Cited by 3 publications

References 64 publications

Attenuating bone loss in osteoporosis: the potential of corylin (CL) as a therapeutic agent

Attenuating bone loss in osteoporosis: the potential of corylin (CL) as a therapeutic agent

Glioma Cells Achieve Malignant Progression by Fusion with Macrophages to Gain High SLC7A5 Expression

Myrislignan targets extracellular signal-regulated kinase (ERK) and modulates mitochondrial function to dampen osteoclastogenesis and ovariectomy-induced osteoporosis

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