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

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Abstract

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.

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Abbreviations

BMP:

Bone morphogenetic protein

BRI:

BMP receptor type I

BRII:

BMP receptor type II

CCN:

Cysteine-rich 61, connective tissue growth factor, nephroblastoma-overexpressed

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Acknowledgements

The author would like to thank all his colleagues in the Department of Oral Rehabilitation and Regenerative Medicine, the Department of Biochemistry and Molecular Dentistry, and the Department of Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, for their generous hosting and all kind assistances during the time taken to accomplish this review. The author also would like to thank Dr. Kristin Sainani A. Professor at Stanford University for her technical assistance.

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Authors and Affiliations

  1. Department of Prosthodontics, Faculty of Oral and Dental Medicine, Fayoum University, Fayoum, Egypt

    Hany Mohamed Khattab

  2. Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Hany Mohamed Khattab & Masaharu Takigawa

  3. Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Satoshi Kubota

  4. Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Takuo Kuboki

  5. Physiological Chemistry II, Theodor-Boveri-Institute for Biocenter of Würzburg University, Würzburg, Germany

    Walter Sebald

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  1. Hany Mohamed Khattab
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Correspondence to Hany Mohamed Khattab.

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Khattab, H.M., Kubota, S., Takigawa, M. et al. The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin. J Bone Miner Metab 37, 199–205 (2019). https://doi.org/10.1007/s00774-018-0925-0

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