BMP and TGFβ use and release in bone regeneration

Zeynep Bal,Joe Kodama,Hideki Yoshikawa,Takashi Kaito,Feza Korkusuz,Junichi Kushioka,Petek Korkusuz

doi:10.3906/sag-2003-127

Zeynep Bal, Joe Kodama + Show 5 more

Open Access

https://doi.org/10.3906/sag-2003-127

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Abstract

A fracture that does not unite in nine months is defined as nonunion. Nonunion is common in fragmented fractures and large bone defects where vascularization is impaired. The distal third of the tibia, the scaphoid bone or the talus fractures are furthermore prone to nonunion. Open fractures and spinal fusion cases also need special monitoring for healing. Bone tissue regeneration can be attained by autografts, allografts, xenografts and synthetic materials, however their limited availability and the increased surgical time as well as the donor site morbidity of autograft use, and lower probability of success, increased costs and disease transmission and immunological reaction probability of allografts oblige us to find better solutions and new grafts to overcome the cons. A proper biomaterial for regeneration should be osteoinductive, osteoconductive, biocompatible and mechanically suitable. Cytokine therapy, where growth factors are introduced either exogenously or triggered endogenously, is one of the commonly used method in bone tissue engineering. Transforming growth factor β (TGFβ) superfamily, which can be divided structurally into two groups as bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs) and TGFβ, activin, Nodal branch, Mullerian hormone, are known to be produced by osteoblasts and other bone cells and present already in bone matrix abundantly, to take roles in bone homeostasis. BMP family, as the biggest subfamily of TGFβ superfamily, is also reported to be the most effective growth factors in bone and development, which makes them one of the most popular cytokines used in bone regeneration. Complications depending on the excess use of growth factors, and pleiotropic functions of BMPs are however the main reasons of why they should be approached with care. In this review, the Smad dependent signaling pathways of TGFβ and BMP families and their relations and the applications in preclinical and clinical studies will be briefly summarized.

Highlights

Trauma, tumor resection, degeneration, deformation may cause bone defects in which the healing process is controlled by cytokines as bone morphogenetic proteins (BMP) or transforming growth factor beta (TGFβ), are a great challenge for regeneration studies [1,2,3,4]
The results showed that TGFβ1 had an inhibitory effect on cell proliferation in a dose-time dependent manner and the maximum inhibition was seen in 40 ng/mL group after 24 h in vitro while it had no effect on cell adhesion to βTCP in any of the dose groups
It is mentioned that Klf4 as one of the factors with Oct4, Sox2, and c-Myc, which are important for redifferentiation of mouse embryonic fibroblasts to mouse ES-like stem cells and can be replaced by BMPs which is a proof of their influence in MET and shows their significant roles in the maintenance and differentiation of pluripotent stem cells [33]

Summary

Introduction

Tumor resection, degeneration, deformation may cause bone defects in which the healing process is controlled by cytokines as bone morphogenetic proteins (BMP) or transforming growth factor beta (TGFβ), are a great challenge for regeneration studies [1,2,3,4]. Osteogenic growth factors or cytokines are generally used in bone tissue engineering due to their osteoinductive abilities because they are able to attract the progenitor cells to the defect area and promote the cell proliferation, migration and endogenous repair mechanisms [1,10] Their effects on the mechanism of bone regeneration via migration, proliferation, differentiation and reconstruction of the extracellular matrix are in time dependent manner [1,4]. Throughout these cytokines, bone morphogenetic proteins (BMPs), as being the biggest subfamily of TGFβ superfamily, are the most commonly used growth factors because they are already present in bone tissue and reported to be necessary for fetal tissue development and fracture repair [1,2,4,6,10,16]. The new bone amount was reported to be almost same within the 0 ng/mL and 40 ng/mL groups

BMP family and its signaling

Results

Conclusion