Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro

Hisashi Ideno, Rieko Takanabe, Akemi Shimada, Kazuhiko Imaizumi, Ryoko Araki, Masumi Abe, Akira Nifuji

    Research output: Contribution to journalArticle

    34 Citations (Scopus)

    Abstract

    Protein related to DAN and cerberus (PRDC) is a secreted protein characterized by a cysteine knot structure, which binds bone morphogenetic proteins (BMPs) and thereby inhibits their binding to BMP receptors. As an extracellular BMP antagonist, PRDC may play critical roles in osteogenesis; however, its expression and function in osteoblastic differentiation have not been determined. Here, we investigated whether PRDC is expressed in osteoblasts and whether it regulates osteogenesis in vitro. PRDC mRNA was found to be expressed in the pre-osteoblasts of embryonic day 18.5 (E18.5) mouse calvariae. PRDC mRNA expression was elevated by treatment with BMP-2 in osteoblastic cells isolated from E18.5 calvariae (pOB cells). Forced expression of PRDC using adenovirus did not affect cell numbers, whereas it suppressed exogenous BMP activity and endogenous levels of phosphorylated Smad1/5/8 protein. Furthermore, PRDC inhibited the expression of bone marker genes and bone-like mineralized matrix deposition in pOB cells. In contrast, the reduction of PRDC expression by siRNA elevated alkaline phosphatase activity, increased endogenous levels of phosphorylated Smad1/5/8 protein, and promoted bone-like mineralized matrix deposition in pOB cells. These results suggest that PRDC expression in osteoblasts suppresses differentiation and that reduction of PRDC expression promotes osteogenesis in vitro. PRDC is accordingly identified as a potential novel therapeutic target for the regulation of bone formation.

    Original languageEnglish
    Pages (from-to)474-484
    Number of pages11
    JournalExperimental Cell Research
    Volume315
    Issue number3
    DOIs
    Publication statusPublished - 2009 Feb 1

    Fingerprint

    Osteogenesis
    Proteins
    Bone Morphogenetic Proteins
    Osteoblasts
    In Vitro Techniques
    Skull
    Bone and Bones
    Bone Morphogenetic Protein Receptors
    Bone Morphogenetic Protein 2
    Messenger RNA
    Adenoviridae
    Small Interfering RNA
    Cysteine
    Alkaline Phosphatase
    Cell Count

    Keywords

    • Antagonist
    • BMP
    • Bone formation
    • Differentiation
    • Osteoblast

    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro. / Ideno, Hisashi; Takanabe, Rieko; Shimada, Akemi; Imaizumi, Kazuhiko; Araki, Ryoko; Abe, Masumi; Nifuji, Akira.

    In: Experimental Cell Research, Vol. 315, No. 3, 01.02.2009, p. 474-484.

    Research output: Contribution to journalArticle

    Ideno, Hisashi ; Takanabe, Rieko ; Shimada, Akemi ; Imaizumi, Kazuhiko ; Araki, Ryoko ; Abe, Masumi ; Nifuji, Akira. / Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro. In: Experimental Cell Research. 2009 ; Vol. 315, No. 3. pp. 474-484.
    @article{90f76d9927d9478d8bbe00193d9060cd,
    title = "Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro",
    abstract = "Protein related to DAN and cerberus (PRDC) is a secreted protein characterized by a cysteine knot structure, which binds bone morphogenetic proteins (BMPs) and thereby inhibits their binding to BMP receptors. As an extracellular BMP antagonist, PRDC may play critical roles in osteogenesis; however, its expression and function in osteoblastic differentiation have not been determined. Here, we investigated whether PRDC is expressed in osteoblasts and whether it regulates osteogenesis in vitro. PRDC mRNA was found to be expressed in the pre-osteoblasts of embryonic day 18.5 (E18.5) mouse calvariae. PRDC mRNA expression was elevated by treatment with BMP-2 in osteoblastic cells isolated from E18.5 calvariae (pOB cells). Forced expression of PRDC using adenovirus did not affect cell numbers, whereas it suppressed exogenous BMP activity and endogenous levels of phosphorylated Smad1/5/8 protein. Furthermore, PRDC inhibited the expression of bone marker genes and bone-like mineralized matrix deposition in pOB cells. In contrast, the reduction of PRDC expression by siRNA elevated alkaline phosphatase activity, increased endogenous levels of phosphorylated Smad1/5/8 protein, and promoted bone-like mineralized matrix deposition in pOB cells. These results suggest that PRDC expression in osteoblasts suppresses differentiation and that reduction of PRDC expression promotes osteogenesis in vitro. PRDC is accordingly identified as a potential novel therapeutic target for the regulation of bone formation.",
    keywords = "Antagonist, BMP, Bone formation, Differentiation, Osteoblast",
    author = "Hisashi Ideno and Rieko Takanabe and Akemi Shimada and Kazuhiko Imaizumi and Ryoko Araki and Masumi Abe and Akira Nifuji",
    year = "2009",
    month = "2",
    day = "1",
    doi = "10.1016/j.yexcr.2008.11.019",
    language = "English",
    volume = "315",
    pages = "474--484",
    journal = "Experimental Cell Research",
    issn = "0014-4827",
    publisher = "Academic Press Inc.",
    number = "3",

    }

    TY - JOUR

    T1 - Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro

    AU - Ideno, Hisashi

    AU - Takanabe, Rieko

    AU - Shimada, Akemi

    AU - Imaizumi, Kazuhiko

    AU - Araki, Ryoko

    AU - Abe, Masumi

    AU - Nifuji, Akira

    PY - 2009/2/1

    Y1 - 2009/2/1

    N2 - Protein related to DAN and cerberus (PRDC) is a secreted protein characterized by a cysteine knot structure, which binds bone morphogenetic proteins (BMPs) and thereby inhibits their binding to BMP receptors. As an extracellular BMP antagonist, PRDC may play critical roles in osteogenesis; however, its expression and function in osteoblastic differentiation have not been determined. Here, we investigated whether PRDC is expressed in osteoblasts and whether it regulates osteogenesis in vitro. PRDC mRNA was found to be expressed in the pre-osteoblasts of embryonic day 18.5 (E18.5) mouse calvariae. PRDC mRNA expression was elevated by treatment with BMP-2 in osteoblastic cells isolated from E18.5 calvariae (pOB cells). Forced expression of PRDC using adenovirus did not affect cell numbers, whereas it suppressed exogenous BMP activity and endogenous levels of phosphorylated Smad1/5/8 protein. Furthermore, PRDC inhibited the expression of bone marker genes and bone-like mineralized matrix deposition in pOB cells. In contrast, the reduction of PRDC expression by siRNA elevated alkaline phosphatase activity, increased endogenous levels of phosphorylated Smad1/5/8 protein, and promoted bone-like mineralized matrix deposition in pOB cells. These results suggest that PRDC expression in osteoblasts suppresses differentiation and that reduction of PRDC expression promotes osteogenesis in vitro. PRDC is accordingly identified as a potential novel therapeutic target for the regulation of bone formation.

    AB - Protein related to DAN and cerberus (PRDC) is a secreted protein characterized by a cysteine knot structure, which binds bone morphogenetic proteins (BMPs) and thereby inhibits their binding to BMP receptors. As an extracellular BMP antagonist, PRDC may play critical roles in osteogenesis; however, its expression and function in osteoblastic differentiation have not been determined. Here, we investigated whether PRDC is expressed in osteoblasts and whether it regulates osteogenesis in vitro. PRDC mRNA was found to be expressed in the pre-osteoblasts of embryonic day 18.5 (E18.5) mouse calvariae. PRDC mRNA expression was elevated by treatment with BMP-2 in osteoblastic cells isolated from E18.5 calvariae (pOB cells). Forced expression of PRDC using adenovirus did not affect cell numbers, whereas it suppressed exogenous BMP activity and endogenous levels of phosphorylated Smad1/5/8 protein. Furthermore, PRDC inhibited the expression of bone marker genes and bone-like mineralized matrix deposition in pOB cells. In contrast, the reduction of PRDC expression by siRNA elevated alkaline phosphatase activity, increased endogenous levels of phosphorylated Smad1/5/8 protein, and promoted bone-like mineralized matrix deposition in pOB cells. These results suggest that PRDC expression in osteoblasts suppresses differentiation and that reduction of PRDC expression promotes osteogenesis in vitro. PRDC is accordingly identified as a potential novel therapeutic target for the regulation of bone formation.

    KW - Antagonist

    KW - BMP

    KW - Bone formation

    KW - Differentiation

    KW - Osteoblast

    UR - http://www.scopus.com/inward/record.url?scp=58149503642&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=58149503642&partnerID=8YFLogxK

    U2 - 10.1016/j.yexcr.2008.11.019

    DO - 10.1016/j.yexcr.2008.11.019

    M3 - Article

    VL - 315

    SP - 474

    EP - 484

    JO - Experimental Cell Research

    JF - Experimental Cell Research

    SN - 0014-4827

    IS - 3

    ER -