Bone morphogenetic proteins and their antagonists: current and emerging clinical uses

被引:96
作者
Ali, Imran H. A. [1 ]
Brazil, Derek P. [1 ]
机构
[1] Queens Univ Belfast, Ctr Med Expt, Belfast BT12 6BA, Antrim, North Ireland
基金
英国生物技术与生命科学研究理事会;
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR-BETA; HUMAN ARTICULAR CHONDROCYTES; KIELIN/CHORDIN-LIKE PROTEIN; PROPOSED PEPTIDE AGONIST; OPEN TIBIAL FRACTURES; OSTEOGENIC PROTEIN-1; OSTEOBLAST DIFFERENTIATION; SIGNAL-TRANSDUCTION; HEPATIC-FIBROSIS;
D O I
10.1111/bph.12724
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Bone morphogenetic proteins (BMPs) are members of the TGF beta superfamily of secreted cysteine knot proteins that includes TGF beta 1, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralized bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes, including limb, kidney, skin, hair and neuronal development, as well as maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment of several pathologies, including bone disorders, kidney and lung fibrosis, and cancer. This review will summarize current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMPs as pharmacological agents for the treatment of bone repair and tissue fibrosis in patients.
引用
收藏
页码:3620 / 3632
页数:13
相关论文
共 159 条
  • [1] THE CONCISE GUIDE TO PHARMACOLOGY 2013/14: CATALYTIC RECEPTORS
    Alexander, Stephen P. H.
    Benson, Helen E.
    Faccenda, Elena
    Pawson, Adam J.
    Sharman, Joanna L.
    Spedding, Michael
    Peters, John A.
    Harmar, Anthony J.
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2013, 170 (08) : 1676 - 1705
  • [2] Aoki H, 2001, J CELL SCI, V114, P1483
  • [3] Extracellular regulation of BMP signaling in vertebrates: A cocktail of modulators
    Balemans, W
    Van Hul, W
    [J]. DEVELOPMENTAL BIOLOGY, 2002, 250 (02) : 231 - 250
  • [4] Effects of protein dose and delivery system on BMP-mediated bone regeneration
    Boerckel, Joel D.
    Kolambkar, Yash M.
    Dupont, Kenneth M.
    Uhrig, Brent A.
    Phelps, Edward A.
    Stevens, Hazel Y.
    Garcia, Andres J.
    Guldberg, Robert E.
    [J]. BIOMATERIALS, 2011, 32 (22) : 5241 - 5251
  • [5] Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells
    Boergermann, J. H.
    Kopf, J.
    Yu, P. B.
    Knaus, P.
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2010, 42 (11) : 1802 - 1807
  • [6] BOHLE A, 1994, EXP NEPHROL, V2, P205
  • [7] Bone morphogenetic protein 7: A broad-spectrum growth factor with multiple target therapeutic potency
    Boon, Mariette R.
    van der Horst, Geertje
    van der Pluijm, Gabri
    Tamsma, Jouke T.
    Smit, Johannes W. A.
    Rensen, Patrick C. N.
    [J]. CYTOKINE & GROWTH FACTOR REVIEWS, 2011, 22 (04) : 221 - 229
  • [8] Bone Morphogenetic Proteins: A critical review
    Bragdon, Beth
    Moseychuk, Oleksandra
    Saldanha, Sven
    King, Daniel
    Julian, Joanne
    Nohe, Anja
    [J]. CELLULAR SIGNALLING, 2011, 23 (04) : 609 - 620
  • [9] Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein
    Brunkow, ME
    Gardner, JC
    Van Ness, J
    Paeper, BW
    Kovacevich, BR
    Proll, S
    Skonier, JE
    Zhao, L
    Sabo, PJ
    Fu, YH
    Alisch, RS
    Gillett, L
    Colbert, T
    Tacconi, P
    Galas, D
    Hamersma, H
    Beighton, P
    Mulligan, JT
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (03) : 577 - 589
  • [10] Gremlin Plays a Key Role in the Pathogenesis of Pulmonary Hypertension
    Cahill, Edwina
    Costello, Christine M.
    Rowan, Simon C.
    Harkin, Susan
    Howell, Katherine
    Leonard, Martin O.
    Southwood, Mark
    Cummins, Eoin P.
    Fitzpatrick, Susan F.
    Taylor, Cormac T.
    Morrell, Nicholas W.
    Martin, Finian
    McLoughlin, Paul
    [J]. CIRCULATION, 2012, 125 (07) : 920 - U241