Antitumor Effect of Sclerostin against Osteosarcoma.

Abstract

Simple SummaryOsteosarcoma is highly variable and heterogeneous, which is one of the reasons for its resistance to treatment. Because osteosarcoma is defined by abnormal bone formation, we hypothesize its suppression could lead to effective treatment for all types of osteosarcomas. Sclerostin is secreted by osteocytes and inhibits the canonical pathway by binding to LRP5/6, thereby suppressing bone formation. The resulting suppression of bone formation leads to bone loss and osteoporosis. Here, we investigated the antitumor effect of sclerostin against osteosarcoma and found that sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells.Various risk factors and causative genes of osteosarcoma have been reported in the literature; however, its etiology remains largely unknown. Bone formation is a shared phenomenon in all types of osteosarcomas, and sclerostin is an extracellular soluble factor secreted by osteocytes that prevents bone formation by inhibiting the Wnt signaling pathway. We aimed to investigate the antitumor effect of sclerostin against osteosarcoma. Osteosarcoma model mice were prepared by transplantation into the dorsal region of C3H/He and BALB/c-nu/nu mice using osteosarcoma cell lines LM8 (murine) and 143B (human), respectively. Cell proliferations were evaluated by using alamarBlue and scratch assays. The migratory ability of the cells was evaluated using a migration assay. Sclerostin was injected intraperitoneally for 7 days to examine the suppression of tumor size and extension of survival. The administration of sclerostin to osteosarcoma cells significantly inhibited the growth and migratory ability of osteosarcoma cells. Kaplan–Meier curves and survival data demonstrated that sclerostin significantly inhibited tumor growth and improved survival. Sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells. Osteosarcoma model mice inhibited tumor growth and prolonged survival periods by the administration of sclerostin. The effect of existing anticancer drugs such as doxorubicin should be investigated for future clinical applications.