Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1‐targeting miRNA‐92a‐1‐5p
| Autor: | Wei-Xiao Fan, Lei Zhou, Zhuo Li, Lin Lei, Lijuan Yu, Yue Zhang, Yanjun Diao, Jiayun Liu, Bingdong Sui, Liu Yang, Xiao-Ke Hao |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Male Histology Osteolysis COL1A1 bone homeostasis Bone Neoplasms exosomes Biology Bone resorption 03 medical and health sciences Mice 0302 clinical medicine Osteoclast miR‐92a‐1‐5p Osteogenesis Cell Line Tumor microRNA medicine Animals Humans Bone Resorption Neoplasm Metastasis Research Articles bone metastasis QH573-671 Bone metastasis Prostatic Neoplasms Osteoblast Cell Biology medicine.disease prostate cancer Microvesicles Collagen Type I alpha 1 Chain Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology medicine.anatomical_structure RAW 264.7 Cells 030220 oncology & carcinogenesis Cancer research Collagen Cytology extracellular vesicles Type I collagen Research Article |
| Zdroj: | Journal of Extracellular Vesicles Journal of Extracellular Vesicles, Vol 10, Iss 3, Pp n/a-n/a (2021) |
| ISSN: | 2001-3078 |
| Popis: | In patients with prostate cancer (PCa), bone lesions appear osteoblastic in radiographs; however, pathological fractures frequently occur in PCa patients, and bone resorption is observed in all metastatic lesions under histopathologic assessment. The mechanisms that balance the activities of osteoblasts and osteoclasts in PCa patients remain unclear. We unexpectedly discovered that PCa exosomes are critical mediators in the regulation of bone homeostasis that results in osteoclastic lesions and thereby promotes tumor growth in bone. We evaluated how exosomes derived from osteoblastic, osteoclastic, and mixed PCa cell lines affect osteoblast and osteoclast differentiation, revealing that all three types of PCa exosomes promoted osteoclastogenesis in vitro and induced osteolysis in vivo. Mechanistically, microRNAs (miRNAs) delivered by PCa exosomes were found to play several key roles in bone homeostasis. Among the delivered miRNAs, miR‐92a‐1‐5p, the most abundant miRNA, downregulated type I collagen expression by directly targeting COL1A1, and thus promoting osteoclast differentiation and inhibiting osteoblastogenesis. Furthermore, PCa exosomes also markedly reduced type I collagen expression in vivo. Our findings not only offer a novel perspective on tumor bone metastasis, where—contrary to our initial hypothesis—exosomes derived from an osteoblastic tumor induce osteoclast differentiation, but also suggest potential therapeutic targets for PCa bone metastasis. |
| Databáze: | OpenAIRE |
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