Stimulation of bone regeneration using bone morphogenetic proteins: modern concepts

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Abstract

It is known that the restoration of fractures or bone defects after trauma is one of the urgent problems of modern orthopedics and traumatology. Bone morphogenetic proteins (BMPs) are a group of growth and differentiation factors that are a large subfamily of the transforming growth factor-β (TGF-β) superfamily. To date, more than 20 types of different BMPs have been identified based on structural similarities, and it has been found that some of them, like BMP-2, -4, -6, -7, and -9, have the most pronounced osteogenic properties. BMPs induce migration, proliferation, and differentiation of undifferentiated mesenchymal stem cells to form osteoblasts and chondroblasts. BMPs have significant inductive effects on various stages of the bone healing process, such as inflammation, angiogenesis, callus formation, and bone remodeling. It is known that recombinant (rh) rhBMP-2 and rhBMP-7 (approved for clinical use in humans by the USA Food and Drug Administration (FDA)), together with the use of bone grafts, they are used to activate reparative osteogenesis in injuries and to replace bone defects in spinal surgery. Therefore, due to its unique properties, the use of BMPs in bone tissue regeneration is one of the most promising and rapidly developing directions in practical medicine. This review discusses the most important concepts regarding the use of BMPs in stimulating bone regeneration, including their mechanisms of action, modes of use, efficacy, and their advantages and disadvantages.

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About the authors

Ural F. Mukhametov

G.G. Kuvatov Republican Clinical Hospital

Email: ufa.rkbkuv@doctorrb.ru
ORCID iD: 0000-0003-3694-3302

MD, Cand. Sci. (Med.)

Russian Federation, 3 Lenin St., Ufa, 450008

Sergey V. Lyulin

Medical Center “Carmel”

Email: carmel74@yandex.ru
ORCID iD: 0000-0002-2549-1059
SPIN-code: 4968-8680
Scopus Author ID: 6701421057
ResearcherId: M-8114-2013

MD, Dr. Sci. (Med.), Professor

Russian Federation, Chelyabinsk

Dmitry Yu. Borzunov

Ural State Medical University

Email: borzunov@bk.ru
ORCID iD: 0000-0003-3720-5467
SPIN-code: 6858-8005
Scopus Author ID: 17433431500

MD, Dr. Sci. (Med.), Professor

Russian Federation, Ekaterinburg

Ilgiz F. Gareev

Bashkir State Medical University

Author for correspondence.
Email: ilgiz_gareev@mail.ru
ORCID iD: 0000-0002-4965-0835
SPIN-code: 3839-0621
Scopus Author ID: 57206481534

MD, PhD

Russian Federation, 3 Lenin St., Ufa, 450008

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2. Fig. 1. The mechanism of action of bone morphogenetic proteins during bone tissue regeneration. Proteins recruit and induce the proliferation of mesenchymal stem cells, which differentiate into chondrocytes and osteoblasts. "+" - stimulating effect; TGF-β - transforming growth factor beta; IL-1 - interleukin-1; IL-6 - interleukin-6; PDGF - platelet growth factor; FGF - fibroblast growth factor

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3. Fig. 2. Signal transmission scheme of bone morphogenetic proteins for induction of osteogenic differentiation of mesenchymal stem cells. ALP - alkaline phosphatase; OSN - osteocalcin; Id1 - inhibitor of DNA binding 1; ERK - kinase regulated by extracellular signals; SMAD - signal converters and transcription modulators

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Copyright (c) 2021 Mukhametov U.F., Lyulin S.V., Borzunov D.Y., Gareev I.F.

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