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Although this system is mainly controlled by alterations in the receptor activator of NF\u2010\u03baB ligand (RANKL), RANKL\u2010based treatment does not prolong the overall survival of patients with PCa bone metastasis. Therefore, it is essential to understand the other interactions between tumour cells and bone\u2010resident cells in the metastatic niche to develop novel treatments. Extracellular vesicles (EVs) play key roles in intercellular communication and actively function in the bone microenvironment. We report that PCa cells corrupt osteoclasts (OCs) via their secretomes, inducing a pathological phenotype. EVs from pathological OCs activate bone\u2010resorbing OCs and suppress bone\u2010forming osteoblasts (OBs), leading to bone destruction. Pathological OCs increased IL\u20101\u03b2 secretion and produced EVs with miR\u20105112 and miR\u20101963, targeting <jats:italic>Parp1<\/jats:italic> in OCs and <jats:italic>Hoxa1<\/jats:italic> in OBs. This led to OC maturation and IL\u20101\u03b2 secretion, and inhibited OB mineralization. Injection of these miRNAs in vivo promoted PCa metastasis\u2010disrupting bone. We report the mediation of EVs from OCs under pathological conditions that modulate the bone metastatic niche independently of RANKL.<\/jats:p>","DOI":"10.1002\/jev2.70091","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:54:54Z","timestamp":1750650894000},"source":"Crossref","is-referenced-by-count":10,"title":["Extracellular Vesicles From Prostate Cancer\u2010Corrupted Osteoclasts Drive a Chain Reaction of Inflammatory Osteolysis and Tumour Progression at the Bone Metastatic Site"],"prefix":"10.1002","volume":"14","author":[{"given":"Takaaki","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Medical Science Tokyo Medical University  Tokyo Japan"},{"name":"Department of Urology Graduate School of Medicine Chiba University  Chiba 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