More than 50% of prostate cancer (PCa) patients have bone metastasis with osteoblastic lesions. MiR-18a-5p is associated with the development and metastasis of PCa

but it remains unclear whether it is involved in osteoblastic lesions. We first found that miR-18a-5p was highly expressed in the bone microenvironment of patients with PCa bone metastases. To address how miR-18a-5p affects PCa osteoblastic lesions

antagonizing miR-18a-5p in PCa cells or pre-osteoblasts inhibited osteoblast differentiation

in vitro

. Moreover

injection of PCa cells with miR-18a-5p inhibition improved bone biomechanical properties and bone mineral mass

in vivo

. Furthermore

miR-18a-5p was transferred to osteoblasts by exosomes derived from PCa cells and targeted the

Hist1h2bc

gene

resulting in Ctnnb1 up-regulation in the Wnt/β-catenin signaling pathway. Translationally

antagomir-18a-5p significantly improved bone biomechanical properties and alleviated sclerotic lesions from osteoblastic metastases in BALB/c nude mice. These data suggest that inhibition of exosome-delivered miR-18a-5p ameliorates PCa-induced osteoblastic lesions.