The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin

被引:9
|
作者
Khattab, Hany Mohamed [1 ,2 ]
Kubota, Satoshi [3 ]
Takigawa, Masaharu [2 ]
Kuboki, Takuo [4 ]
Sebald, Walter [5 ]
机构
[1] Fayoum Univ, Fac Oral & Dent Med, Dept Prosthodont, Al Fayyum, Egypt
[2] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Adv Res Ctr Oral & Craniofacial Sci, Okayama, Japan
[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Biochem & Mol Dent, Okayama, Japan
[4] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Rehabil & Regenerat Med, Okayama, Japan
[5] Wurzburg Univ, Bioctr, Theodor Boveri Inst, Physiol Chem 2, Wurzburg, Germany
基金
日本学术振兴会;
关键词
BMP-2; BMP antagonist; L51P; BMP negative feedback; TISSUE-GROWTH-FACTOR; BONE-FORMATION; OSTEOBLAST DIFFERENTIATION; TGF-BETA; MOLECULAR RECOGNITION; IN-VITRO; ANTAGONISTS; SCLEROSTEOSIS; PROLIFERATION; EXPRESSION;
D O I
10.1007/s00774-018-0925-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The antagonist-specific regulation in tissue engineering constitutes important attempts to achieve an improved and rapid bone regeneration by controlling the natural biological response of the natural body growth factors. L51P is molecularly engineered bone morphogentic protein-2 (BMP-2) variant with a substitution of the 51st leucine with a proline residue. L51P is deficient in BMP receptor binding, but maintains its structure and affinity for inhibitory proteins such as noggin, chordin, and gremlin. These modifications convert the BMP-2 variant L51P into a receptor-inactive inhibitor of BMP antagonists. This current approach may prevent the uncontrolled bone overgrowth using high concentration of BMPs and thus regulates the possible growth factor's high-dose side effects. Exploring of L51P biological functions is required to broad our understanding of BMP mutant biological functions and their potential clinical applications. The progress of L51P researches would hopefully lead to the development of multiple applications for using the L51P in bone and fracture healing disorders.
引用
收藏
页码:199 / 205
页数:7
相关论文
共 28 条
  • [1] The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin
    Hany Mohamed Khattab
    Satoshi Kubota
    Masaharu Takigawa
    Takuo Kuboki
    Walter Sebald
    [J]. Journal of Bone and Mineral Metabolism, 2019, 37 : 199 - 205
  • [2] L51P, a BMP-2 Antagonist Inhibitor, Enhances the Osteoiduction of BMP-2 by a Negative Feedback Regulation
    Khattab, Hany
    Ono, Mitsu
    Sonoyama, Wataru
    Oida, Yasutaka
    Shinkawa, Shigehiko
    Maekawa, Kenji
    Sugama, Kazushige
    Sebald, Walter
    Kuboki, Takuo
    [J]. JOURNAL OF BONE AND MINERAL RESEARCH, 2013, 28
  • [3] The pro-form of BMP-2 interferes with BMP-2 signalling by competing with BMP-2 for IA receptor binding
    Hauburger, Anja
    von Einem, Sabrina
    Schwaerzer, Gerburg K.
    Buttstedt, Anja
    Zebisch, Matthias
    Schraeml, Michael
    Hortschansky, Peter
    Knaus, Petra
    Schwarz, Elisabeth
    [J]. FEBS JOURNAL, 2009, 276 (21) : 6386 - 6398
  • [4] Osteogenesis with BMP-2 variant L51P in a critical size defect model in rats
    Sebald, Hans-Joerg
    Siegrist, Mark
    Klenke, Frank
    Hofstetter, Willy
    Sebald, Walter
    [J]. BONE, 2010, 46 : S80 - S81
  • [5] Molecular recognition of BMP-2 and BMP receptor IA
    Sascha Keller
    Joachim Nickel
    Jin-Li Zhang
    Walter Sebald
    Thomas D Mueller
    [J]. Nature Structural & Molecular Biology, 2004, 11 : 481 - 488
  • [6] Molecular recognition of BMP-2 and BMP receptor IA
    Keller, S
    Nickel, J
    Zhang, JL
    Sebald, W
    Mueller, TD
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2004, 11 (05) : 481 - 488
  • [7] The BMP2 antagonist inhibitor L51P enhances the osteogenic potential of BMP2 by simultaneous and delayed synergism
    Khattab, Hany Mohamed
    Ono, Mitsuaki
    Sonoyama, Wataru
    Oida, Yasutaka
    Shinkawa, Shigehiko
    Yoshioka, Yuya
    Maekawa, Kenji
    Tabata, Yasuhiko
    Sugama, Kazushige
    Sebald, Walter
    Kuboki, Talmo
    [J]. BONE, 2014, 69 : 165 - 173
  • [8] Heparin inhibits BMP-2 osteogenic bioactivity by binding to both BMP-2 and BMP receptor
    Kanzaki, Shin
    Takahashi, Tetsu
    Kanno, Takahiro
    Ariyoshi, Wataru
    Shinmyouzu, Kouhei
    Tujisawa, Toshiyuki
    Nishihara, Tatsuji
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2008, 216 (03) : 844 - 850
  • [9] Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP-2
    Kirsch, T
    Nickel, J
    Sebald, W
    [J]. FEBS LETTERS, 2000, 468 (2-3) : 215 - 219
  • [10] The BMP-2: BMP receptor IA complex: structural evidence for type I/type II receptor discrimination
    Kirsch, T.
    Nickel, J.
    Sebald, W.
    Dreyer, M.
    [J]. ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES, 2000, 56 : S292 - S292