The study aims to investigate the effects of Periostin gene silencing on tumor microenvironment and bone metastasis via the integrin-signaling pathway in lung cancer (LC). LC patients were divided into bone metastasis and non-bone metastasis groups; Healthy volunteers were selected as normal group. ELISA was performed to detect serum Periostin levels and plasma calcium ion concentration. SBC-5 cells were assigned into blank group (without transfection), negative control (NC) group (transfected with empty plasmid), si-Periostin group (transfectedwith si-Periostin plasmid), si-Integrin-alpha v beta 3 group (transfected with Integrin-alpha v beta 3 siRNA plasmid) and si-Periostin+ si-Integrin-alpha v beta 3 group (transfectedwith si-Periostin and si-Integrin-alpha v beta 3 plasmid). qRT-PCR andWestern blotting were performed to determine mRNA and protein expression of Periostin, metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins. CCK-8, scratch test and transwell assay were applied to detect cell proliferation, migration and invasion respectively. Nude mouse models of LC bone metastasis were established. TRAP Staining was employed to measure the number of osteoclasts. Bone metastasis group exhibited higher levels of Periostin compared to normal and non-bone metastasis groups. Si-Periostin, si-Integrin-alpha v beta 3 and si-Periostin + si-Integrin-alpha v beta 3 groups showed decreased Periostin expression, proliferation rate, migration distance, invasive cells, and expressions of metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins compared to blank and NC groups. Similarly, number of osteoclasts and expression of integrin signaling pathway-related proteins were decreased, and bone injury and calcium ion concentration were reduced. The study demonstrated that down-regulation of Periostin expression modulated tumor microenvironment and inhibited bone metastasis by blocking integrin-signaling pathway in LC. (C) 2017 Elsevier Inc. All rights reserved.