Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice

作者：Jie Huang, Hao Yin, Shan‐Shan Rao, Ping-Li Xie, Xu Cao, T.Lakshmi Rao, Shuying Liu, Zhenxing Wang, Jia Cao, Yin Hu, Yan Zhang, Juan Luo, Yi‐Juan Tan, Zhengzhao Liu, Ben Wu, Xiong‐Ke Hu, Tuan‐Hui Chen, Chun‐Yuan Chen, Hui Xie · 发表于：Theranostics · 年份：2018 · DOI：10.7150/thno.22144 · 被引用次数：139 · 研究领域：Bone Metabolism and Diseases、Bone health and treatments、Bone Tissue Engineering Materials

Recently, researchers identified a distinct vessel subtype called type H vessels that couple angiogenesis and osteogenesis.We previously found that type H vessels are reduced in ovariectomy (OVX)-induced osteoporotic mice, and preosteoclasts are able to secrete platelet-derived growth factor-BB (PDGF-BB) to stimulate type H vessel formation and thereby to promote osteogenesis.This study aimed to explore whether harmine, a β-carboline alkaloid, is capable of preventing bone loss in OVX mice by promoting preosteoclast PDGF-BB-induced type H vessel formation.Methods: The impact of harmine on osteoclastogenesis of RANKL-stimulated RAW264.7 cells was verified by gene expression analysis and tartrate-resistant acid phosphatase (TRAP) staining.Enzyme-linked immunosorbent assay (ELISA) was conducted to test PDGF-BB production by preosteoclasts.A series of angiogenesis-related assays in vitro were performed to assess the pro-angiogenic effects of the conditioned media from RANKL-stimulated RAW264.7 cells treated with or without harmine.Meanwhile, the role of PDGF-BB in this process was determined.In vivo, OVX mice were intragastrically administrated with harmine emulsion or an equal volume of vehicle. 2 months later, bone samples were collected for µCT, histological, immunohistochemical and immunofluorescent analyses to evaluate bone mass, osteogenic and osteoclastic activities, as well as the numbers of type H vessels. Bone marrow PDGF-BB concentrations were assessed by ELISA.Results...