CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling

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CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling. / Abdallah, Basem M.; Figeac, Florence; Larsen, Kenneth H.; Ditzel, Nicholas; Keshari, Pankaj; Isa, Adiba; Jafari Kermani, Abbas; Andersen, Thomas L; Delaisse, Jean-Marie; Goshima, Yoshio; Ohshima, Toshio; Kassem, Moustapha.

I: Journal of Bone and Mineral Research, Bind 32, Nr. 5, 05.2017, s. 913-926.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Abdallah, BM, Figeac, F, Larsen, KH, Ditzel, N, Keshari, P, Isa, A, Jafari Kermani, A, Andersen, TL, Delaisse, J-M, Goshima, Y, Ohshima, T & Kassem, M 2017, 'CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling', Journal of Bone and Mineral Research, bind 32, nr. 5, s. 913-926. https://doi.org/10.1002/jbmr.3069

APA

Abdallah, B. M., Figeac, F., Larsen, K. H., Ditzel, N., Keshari, P., Isa, A., Jafari Kermani, A., Andersen, T. L., Delaisse, J-M., Goshima, Y., Ohshima, T., & Kassem, M. (2017). CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling. Journal of Bone and Mineral Research, 32(5), 913-926. https://doi.org/10.1002/jbmr.3069

Vancouver

Abdallah BM, Figeac F, Larsen KH, Ditzel N, Keshari P, Isa A o.a. CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling. Journal of Bone and Mineral Research. 2017 maj;32(5):913-926. https://doi.org/10.1002/jbmr.3069

Author

Abdallah, Basem M. ; Figeac, Florence ; Larsen, Kenneth H. ; Ditzel, Nicholas ; Keshari, Pankaj ; Isa, Adiba ; Jafari Kermani, Abbas ; Andersen, Thomas L ; Delaisse, Jean-Marie ; Goshima, Yoshio ; Ohshima, Toshio ; Kassem, Moustapha. / CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling. I: Journal of Bone and Mineral Research. 2017 ; Bind 32, Nr. 5. s. 913-926.

Bibtex

@article{b54b6292dcea40cab8b329257a7ee402,

title = "CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling",

abstract = "We identified the neuroprotein collapsing response mediator protein-4 (CRMP4) as a noncanonical osteogenic factor that regulates the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells [mBMSCs]) into osteoblastic cells. CRMP4 is the only member of the CRMP1-CRMP5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain-of-function and loss-of-function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation. In addition, Crmp4-deficient mice (Crmp4(-/-) ) displayed a 40% increase in bone mass, increased mineral apposition rate, and bone formation rate, compared to wild-type controls. Increased bone mass in Crmp4(-/-) mice was associated with enhanced BMP2 signaling and BMP2-induced osteoblast differentiation in Crmp4(-/-) osteoblasts (OBs). Furthermore, Crmp4(-/-) OBs exhibited enhanced activation of RhoA/focal adhesion kinase (FAK) signaling that led to cytoskeletal changes with increased cell spreading. In addition, Crmp4(-/-) OBs exhibited increased cell proliferation that was mediated via inhibiting cyclin-dependent kinase inhibitor 1B, p27(Kip1) and upregulating cyclin D1 expression which are targets of RhoA signaling pathway. Our findings identify CRMP4 as a novel negative regulator of osteoblast differentiation. {\textcopyright} 2017 American Society for Bone and Mineral Research.[on SciFinder (R)]",

keywords = "bone remodeling, crmp4, dpysl3, osteoblast, osteoporosis",

author = "Abdallah, {Basem M.} and Florence Figeac and Larsen, {Kenneth H.} and Nicholas Ditzel and Pankaj Keshari and Adiba Isa and {Jafari Kermani}, Abbas and Andersen, {Thomas L} and Jean-Marie Delaisse and Yoshio Goshima and Toshio Ohshima and Moustapha Kassem",

year = "2017",

month = may,

doi = "10.1002/jbmr.3069",

language = "English",

volume = "32",

pages = "913--926",

journal = "Journal of Bone and Mineral Research",

issn = "0884-0431",

publisher = "Wiley-Blackwell",

number = "5",

}

RIS

TY - JOUR

T1 - CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling

AU - Abdallah, Basem M.

AU - Figeac, Florence

AU - Larsen, Kenneth H.

AU - Ditzel, Nicholas

AU - Keshari, Pankaj

AU - Isa, Adiba

AU - Jafari Kermani, Abbas

AU - Andersen, Thomas L

AU - Delaisse, Jean-Marie

AU - Goshima, Yoshio

AU - Ohshima, Toshio

AU - Kassem, Moustapha

PY - 2017/5

Y1 - 2017/5

N2 - We identified the neuroprotein collapsing response mediator protein-4 (CRMP4) as a noncanonical osteogenic factor that regulates the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells [mBMSCs]) into osteoblastic cells. CRMP4 is the only member of the CRMP1-CRMP5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain-of-function and loss-of-function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation. In addition, Crmp4-deficient mice (Crmp4(-/-) ) displayed a 40% increase in bone mass, increased mineral apposition rate, and bone formation rate, compared to wild-type controls. Increased bone mass in Crmp4(-/-) mice was associated with enhanced BMP2 signaling and BMP2-induced osteoblast differentiation in Crmp4(-/-) osteoblasts (OBs). Furthermore, Crmp4(-/-) OBs exhibited enhanced activation of RhoA/focal adhesion kinase (FAK) signaling that led to cytoskeletal changes with increased cell spreading. In addition, Crmp4(-/-) OBs exhibited increased cell proliferation that was mediated via inhibiting cyclin-dependent kinase inhibitor 1B, p27(Kip1) and upregulating cyclin D1 expression which are targets of RhoA signaling pathway. Our findings identify CRMP4 as a novel negative regulator of osteoblast differentiation. © 2017 American Society for Bone and Mineral Research.[on SciFinder (R)]

AB - We identified the neuroprotein collapsing response mediator protein-4 (CRMP4) as a noncanonical osteogenic factor that regulates the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells [mBMSCs]) into osteoblastic cells. CRMP4 is the only member of the CRMP1-CRMP5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain-of-function and loss-of-function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation. In addition, Crmp4-deficient mice (Crmp4(-/-) ) displayed a 40% increase in bone mass, increased mineral apposition rate, and bone formation rate, compared to wild-type controls. Increased bone mass in Crmp4(-/-) mice was associated with enhanced BMP2 signaling and BMP2-induced osteoblast differentiation in Crmp4(-/-) osteoblasts (OBs). Furthermore, Crmp4(-/-) OBs exhibited enhanced activation of RhoA/focal adhesion kinase (FAK) signaling that led to cytoskeletal changes with increased cell spreading. In addition, Crmp4(-/-) OBs exhibited increased cell proliferation that was mediated via inhibiting cyclin-dependent kinase inhibitor 1B, p27(Kip1) and upregulating cyclin D1 expression which are targets of RhoA signaling pathway. Our findings identify CRMP4 as a novel negative regulator of osteoblast differentiation. © 2017 American Society for Bone and Mineral Research.[on SciFinder (R)]

KW - bone remodeling

KW - crmp4

KW - dpysl3

KW - osteoblast

KW - osteoporosis

U2 - 10.1002/jbmr.3069

DO - 10.1002/jbmr.3069

M3 - Journal article

C2 - 28019696

VL - 32

SP - 913

EP - 926

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 5

ER -

ID: 173291061