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

Jie Huang, Hao Yin, Shan Shan Rao, Ping Li Xie, Xu Cao, Tai Rao, Shu Ying Liu, Zhen Xing Wang, Jia Cao, Yin Hu, Yan Zhang, Juan Luo, Yi Juan Tan, Zheng Zhao Liu, Ben Wu, Xiong Ke Hu, Tuan Hui Chen, Chun Yuan Chen, Hui Xie

Research output: Contribution to journalArticle

Abstract

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: Exposure of RANKL-stimulated RAW264.7 cells to harmine enhanced the formation of preosteoclasts and the production of PDGF-BB. Harmine augmented the ability of RANKL-stimulated RAW264.7 cells to promote angiogenesis of endothelial cells, whereas the effect was blocked by PDGF-BB inhibition. In vivo, the oral administration of harmine emulsion to OVX mice resulted in enhanced trabecular bone mass and osteogenic responses, increased numbers of preosteoclasts, as well as reduced numbers of osteoclasts and fat cells. Moreover, OVX mice treated with harmine exhibited higher levels of bone marrow PDGF-BB and much more type H vessels in bone. Conclusion: Harmine may exert bone-sparing effects by suppression of osteoclast formation and promotion of preosteoclast PDGF-BB-induced angiogenesis.

Original languageEnglish (US)
Pages (from-to)2435-2446
Number of pages12
JournalTheranostics
Volume8
Issue number9
DOIs
StatePublished - Jan 1 2018

Fingerprint

Harmine
Osteogenesis
Bone and Bones
Osteoclasts
Emulsions
Bone Marrow
Enzyme-Linked Immunosorbent Assay
platelet-derived growth factor BB
Carbolines
Ovariectomy
Conditioned Culture Medium
Alkaloids
Adipocytes
Oral Administration
Endothelial Cells
Research Personnel

Keywords

  • Angiogenesis
  • Harmine
  • Osteogenesis
  • PDGF-BB
  • Preosteoclast

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Huang, J., Yin, H., Rao, S. S., Xie, P. L., Cao, X., Rao, T., ... Xie, H. (2018). Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice. Theranostics, 8(9), 2435-2446. https://doi.org/10.7150/thno.22144

Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice. / Huang, Jie; Yin, Hao; Rao, Shan Shan; Xie, Ping Li; Cao, Xu; Rao, Tai; Liu, Shu Ying; Wang, Zhen Xing; Cao, Jia; Hu, Yin; Zhang, Yan; Luo, Juan; Tan, Yi Juan; Liu, Zheng Zhao; Wu, Ben; Hu, Xiong Ke; Chen, Tuan Hui; Chen, Chun Yuan; Xie, Hui.

In: Theranostics, Vol. 8, No. 9, 01.01.2018, p. 2435-2446.

Research output: Contribution to journalArticle

Huang, J, Yin, H, Rao, SS, Xie, PL, Cao, X, Rao, T, Liu, SY, Wang, ZX, Cao, J, Hu, Y, Zhang, Y, Luo, J, Tan, YJ, Liu, ZZ, Wu, B, Hu, XK, Chen, TH, Chen, CY & Xie, H 2018, 'Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice', Theranostics, vol. 8, no. 9, pp. 2435-2446. https://doi.org/10.7150/thno.22144
Huang, Jie ; Yin, Hao ; Rao, Shan Shan ; Xie, Ping Li ; Cao, Xu ; Rao, Tai ; Liu, Shu Ying ; Wang, Zhen Xing ; Cao, Jia ; Hu, Yin ; Zhang, Yan ; Luo, Juan ; Tan, Yi Juan ; Liu, Zheng Zhao ; Wu, Ben ; Hu, Xiong Ke ; Chen, Tuan Hui ; Chen, Chun Yuan ; Xie, Hui. / Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice. In: Theranostics. 2018 ; Vol. 8, No. 9. pp. 2435-2446.
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T1 - Harmine enhances type H vessel formation and prevents bone loss in ovariectomized mice

AU - Huang, Jie

AU - Yin, Hao

AU - Rao, Shan Shan

AU - Xie, Ping Li

AU - Cao, Xu

AU - Rao, Tai

AU - Liu, Shu Ying

AU - Wang, Zhen Xing

AU - Cao, Jia

AU - Hu, Yin

AU - Zhang, Yan

AU - Luo, Juan

AU - Tan, Yi Juan

AU - Liu, Zheng Zhao

AU - Wu, Ben

AU - Hu, Xiong Ke

AU - Chen, Tuan Hui

AU - Chen, Chun Yuan

AU - Xie, Hui

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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: Exposure of RANKL-stimulated RAW264.7 cells to harmine enhanced the formation of preosteoclasts and the production of PDGF-BB. Harmine augmented the ability of RANKL-stimulated RAW264.7 cells to promote angiogenesis of endothelial cells, whereas the effect was blocked by PDGF-BB inhibition. In vivo, the oral administration of harmine emulsion to OVX mice resulted in enhanced trabecular bone mass and osteogenic responses, increased numbers of preosteoclasts, as well as reduced numbers of osteoclasts and fat cells. Moreover, OVX mice treated with harmine exhibited higher levels of bone marrow PDGF-BB and much more type H vessels in bone. Conclusion: Harmine may exert bone-sparing effects by suppression of osteoclast formation and promotion of preosteoclast PDGF-BB-induced angiogenesis.

AB - 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: Exposure of RANKL-stimulated RAW264.7 cells to harmine enhanced the formation of preosteoclasts and the production of PDGF-BB. Harmine augmented the ability of RANKL-stimulated RAW264.7 cells to promote angiogenesis of endothelial cells, whereas the effect was blocked by PDGF-BB inhibition. In vivo, the oral administration of harmine emulsion to OVX mice resulted in enhanced trabecular bone mass and osteogenic responses, increased numbers of preosteoclasts, as well as reduced numbers of osteoclasts and fat cells. Moreover, OVX mice treated with harmine exhibited higher levels of bone marrow PDGF-BB and much more type H vessels in bone. Conclusion: Harmine may exert bone-sparing effects by suppression of osteoclast formation and promotion of preosteoclast PDGF-BB-induced angiogenesis.

KW - Angiogenesis

KW - Harmine

KW - Osteogenesis

KW - PDGF-BB

KW - Preosteoclast

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