NPNT is expressed by osteoblasts and mediates angiogenesis via the activation of extracellular signal-regulated kinase

Vincent Kuek, Z. Yang, Shek Chim, Sipin Zhu, H. Xu, Siu To Chow, Jennifer Tickner, V. Rosen, Wendy Erber, X. Li, Q. An, Y. Qian, Jiake Xu

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    Abstract

    © 2016 The Author(s).Angiogenesis plays an important role in bone development and remodeling and is mediated by a plethora of potential angiogenic factors. However, data regarding specific angiogenic factors that are secreted within the bone microenvironment to regulate osteoporosis is lacking. Here, we report that Nephronectin (NPNT), a member of the epidermal growth factor (EGF) repeat superfamily proteins and a homologue of EGFL6, is expressed in osteoblasts. Intriguingly, the gene expression of NPNT is reduced in the bone of C57BL/6J ovariectomised mice and in osteoporosis patients. In addition, the protein levels of NPNT and CD31 are also found to be reduced in the tibias of OVX mice. Exogenous addition of mouse recombinant NPNT on endothelial cells stimulates migration and tube-like structure formation in vitro. Furthermore, NPNT promotes angiogenesis in an ex vivo fetal mouse metatarsal angiogenesis assay. We show that NPNT stimulates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated kinase (MAPK) in endothelial cells. Inhibition of ERK1/2 impaired NPNT-induced endothelial cell migration, tube-like structure formation and angiogenesis. Taken together, these results demonstrate that NPNT is a paracrine angiogenic factor and may play a role in pathological osteoporosis. This may lead to new targets for treatment of bone diseases and injuries.
    Original languageEnglish
    Article number36210
    Pages (from-to)1-13
    Number of pages13
    JournalScientific Reports
    Volume6
    DOIs
    Publication statusPublished - 26 Oct 2016

    Fingerprint

    Extracellular Signal-Regulated MAP Kinases
    Osteoblasts
    Angiogenesis Inducing Agents
    Osteoporosis
    Mitogen-Activated Protein Kinase 3
    Endothelial Cells
    Mitogen-Activated Protein Kinase 1
    Cell Movement
    Bone and Bones
    Metatarsal Bones
    nephronectin
    Bone Remodeling
    Bone Diseases
    Bone Development
    Mitogen-Activated Protein Kinase Kinases
    Tibia
    Mitogens
    Epidermal Growth Factor
    Proteins
    Phosphorylation

    Cite this

    Kuek, Vincent ; Yang, Z. ; Chim, Shek ; Zhu, Sipin ; Xu, H. ; Chow, Siu To ; Tickner, Jennifer ; Rosen, V. ; Erber, Wendy ; Li, X. ; An, Q. ; Qian, Y. ; Xu, Jiake. / NPNT is expressed by osteoblasts and mediates angiogenesis via the activation of extracellular signal-regulated kinase. In: Scientific Reports. 2016 ; Vol. 6. pp. 1-13.
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    abstract = "{\circledC} 2016 The Author(s).Angiogenesis plays an important role in bone development and remodeling and is mediated by a plethora of potential angiogenic factors. However, data regarding specific angiogenic factors that are secreted within the bone microenvironment to regulate osteoporosis is lacking. Here, we report that Nephronectin (NPNT), a member of the epidermal growth factor (EGF) repeat superfamily proteins and a homologue of EGFL6, is expressed in osteoblasts. Intriguingly, the gene expression of NPNT is reduced in the bone of C57BL/6J ovariectomised mice and in osteoporosis patients. In addition, the protein levels of NPNT and CD31 are also found to be reduced in the tibias of OVX mice. Exogenous addition of mouse recombinant NPNT on endothelial cells stimulates migration and tube-like structure formation in vitro. Furthermore, NPNT promotes angiogenesis in an ex vivo fetal mouse metatarsal angiogenesis assay. We show that NPNT stimulates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated kinase (MAPK) in endothelial cells. Inhibition of ERK1/2 impaired NPNT-induced endothelial cell migration, tube-like structure formation and angiogenesis. Taken together, these results demonstrate that NPNT is a paracrine angiogenic factor and may play a role in pathological osteoporosis. This may lead to new targets for treatment of bone diseases and injuries.",
    author = "Vincent Kuek and Z. Yang and Shek Chim and Sipin Zhu and H. Xu and Chow, {Siu To} and Jennifer Tickner and V. Rosen and Wendy Erber and X. Li and Q. An and Y. Qian and Jiake Xu",
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    NPNT is expressed by osteoblasts and mediates angiogenesis via the activation of extracellular signal-regulated kinase. / Kuek, Vincent; Yang, Z.; Chim, Shek; Zhu, Sipin; Xu, H.; Chow, Siu To; Tickner, Jennifer; Rosen, V.; Erber, Wendy; Li, X.; An, Q.; Qian, Y.; Xu, Jiake.

    In: Scientific Reports, Vol. 6, 36210, 26.10.2016, p. 1-13.

    Research output: Contribution to journalArticle

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    AU - Yang, Z.

    AU - Chim, Shek

    AU - Zhu, Sipin

    AU - Xu, H.

    AU - Chow, Siu To

    AU - Tickner, Jennifer

    AU - Rosen, V.

    AU - Erber, Wendy

    AU - Li, X.

    AU - An, Q.

    AU - Qian, Y.

    AU - Xu, Jiake

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    N2 - © 2016 The Author(s).Angiogenesis plays an important role in bone development and remodeling and is mediated by a plethora of potential angiogenic factors. However, data regarding specific angiogenic factors that are secreted within the bone microenvironment to regulate osteoporosis is lacking. Here, we report that Nephronectin (NPNT), a member of the epidermal growth factor (EGF) repeat superfamily proteins and a homologue of EGFL6, is expressed in osteoblasts. Intriguingly, the gene expression of NPNT is reduced in the bone of C57BL/6J ovariectomised mice and in osteoporosis patients. In addition, the protein levels of NPNT and CD31 are also found to be reduced in the tibias of OVX mice. Exogenous addition of mouse recombinant NPNT on endothelial cells stimulates migration and tube-like structure formation in vitro. Furthermore, NPNT promotes angiogenesis in an ex vivo fetal mouse metatarsal angiogenesis assay. We show that NPNT stimulates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated kinase (MAPK) in endothelial cells. Inhibition of ERK1/2 impaired NPNT-induced endothelial cell migration, tube-like structure formation and angiogenesis. Taken together, these results demonstrate that NPNT is a paracrine angiogenic factor and may play a role in pathological osteoporosis. This may lead to new targets for treatment of bone diseases and injuries.

    AB - © 2016 The Author(s).Angiogenesis plays an important role in bone development and remodeling and is mediated by a plethora of potential angiogenic factors. However, data regarding specific angiogenic factors that are secreted within the bone microenvironment to regulate osteoporosis is lacking. Here, we report that Nephronectin (NPNT), a member of the epidermal growth factor (EGF) repeat superfamily proteins and a homologue of EGFL6, is expressed in osteoblasts. Intriguingly, the gene expression of NPNT is reduced in the bone of C57BL/6J ovariectomised mice and in osteoporosis patients. In addition, the protein levels of NPNT and CD31 are also found to be reduced in the tibias of OVX mice. Exogenous addition of mouse recombinant NPNT on endothelial cells stimulates migration and tube-like structure formation in vitro. Furthermore, NPNT promotes angiogenesis in an ex vivo fetal mouse metatarsal angiogenesis assay. We show that NPNT stimulates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated kinase (MAPK) in endothelial cells. Inhibition of ERK1/2 impaired NPNT-induced endothelial cell migration, tube-like structure formation and angiogenesis. Taken together, these results demonstrate that NPNT is a paracrine angiogenic factor and may play a role in pathological osteoporosis. This may lead to new targets for treatment of bone diseases and injuries.

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