INTRODUCTIONrnBone is the most common metastatic site for castration-resistant prostate cancer.1 Nearly 70％–80％ of the patients with advanced-stage prostate cancer (PCa) develop skeletal metastases which remains as the most common cause of deaths in these patients. The 1-year survival rate in patients with metastatic PCa without incidence in bone is at nearly 87％, which is reduced to 47％ in patients with bone metastasis.2 Only 3％ of patients with bone metastasis survive after 5 years compared to 56％ patients without bone metastasis.3 In addition, PCa patients with bone metastasis frequently suffer from skeletal-related events (SREs) such as severe bone pain, pathologic fractures, spinal cord and nerve compression syndromes, and hypercalcemia.4–5 Current treatment strategy for PCa patients with metastatic bone disease includes taxane-based chemotherapy, which can effectively limit the progression of the disease for a short time period but patients eventually relapse within the first year of treatment.6–9 To date, bone metastasis remains as a frequent and fatal complication in PCa patients, and its management is a clinical challenge. Thus, new molecular target(s) that can be therapeutically exploited are needed to improve patient outcomes. A major consideration in this effort is that treatment strategies for PCa cells metastasized to bone are also likely to influence the normal bone cells present at the site of metastatic lesions. This is because the metastatic disease results from an interplay between cancer cells and the bone cells namely osteoblasts and osteoclasts, which contributes to a vicious cycle that provides a fertile soil for metastatic growth of cancer cells in the bone.1,10–11 Radiographic studies of PCa patients with bone involvement characterized bone metastases as osteoblastic lesions as opposed to osteolytic lesions with decreased bone mineral density.12 In fact, PCa bone metastases show a heterogeneous blend of osteoblastic and osteolytic functions with the balance shifted to favor osteoblastic metastasis. Because of this multifaceted interplay between PCa cells and bone cells, it is important to test how a potential therapy against metastatic PCa cells can influence the function of bone cells.