RGD‐modified dihydrolipoamide dehydrogenase as a molecular bridge for enhancing the adhesion of bone forming cells to titanium dioxide implant surfaces

Dayan, Avraham; Lamed, Raphael; Benayahu, Dafna; Fleminger, Gideon

doi:10.1002/jbm.a.36570

Cited by 11 publications

(10 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This layer affects both chemical inertness and biocompatibility and bone-implant interactions. 120 Several surface oxidation methods, such as anodic oxidation, 121 acid electrochemical treatment, 122,123 plasma spray deposition, 124 and thermal oxidation, 35,120,125,126 are used to improve the functionality of the TiO 2 layer. 120 The temperature and the duration of the thermal treatment determine both the thickness and the crystallinity of the TiO 2 layer.…”

Section: Dldh Rgd As a Molecular Bridge Between Tio 2 -Based Medical Implants And Bone Forming Cells For Osseointegration Enhancementmentioning

confidence: 99%

“…In addition, we describe the construction of DLDH derivatized with Arginine-Glycine-Aspartic acid (RGD, DLDH RGD ) which enabled the enzyme's interaction with integrin-rich cells 12 (eg, cancer cells). This enabled some potential medical applications in the fields of oseointegration of Ti-based implants 35 and photodynamic therapy 36 where DLDH RGD served as a molecular bridge allowing to reach higher proximity of the TiO 2 with integrin-rich tissues and cells. Furthermore, DLDH RGD alone was shown to be incorporated into cancer cells by integrin-assisted endocytosis 37 and, by virtue of its ROS-generation capability, enabling cancer cell apoptotic destruction.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The moonlighting activities of dihydrolipoamide dehydrogenase: Biotechnological and biomedical applications

Fleminger

Dayan

2021

J of Molecular Recognition

Self Cite

View full text Add to dashboard Cite

Dihydrolipoamide dehydrogenase (DLDH) is a homodimeric flavin-dependent enzyme that catalyzes the NAD + -dependent oxidation of dihydrolipoamide. The enzyme is part of several multi-enzyme complexes such as the Pyruvate Dehydrogenase system that transforms pyruvate into acetyl-co-A. Concomitantly with its redox activity, DLDH produces Reactive Oxygen Species (ROS), which are involved in cellular apoptotic processes. DLDH possesses several moonlighting functions. One of these is the capacity to adhere to metal-oxides surfaces. This was first exemplified by the presence of an exocellular form of the enzyme on the cell-wall surface of Rhodococcus ruber. This capability was evolutionarily conserved and identified in the human, mitochondrial, DLDH. The enzyme was modified with Arg-Gly-Asp (RGD) groups, which enabled its interaction with integrin-rich cancer cells followed by "integrin-assisted-endocytosis." This allowed harnessing the enzyme for cancer therapy. Combining the TiO 2 -binding property with DLDH's ROS-production, enabled us to develop several medical applications including improving oesseointegration of TiO 2 -based implants and photodynamic treatment for melanoma. The TiO 2 -binding sites of both the bacterial and human DLDH's were identified on the proteins' molecules at regions that overlap with the binding site of E3-binding protein (E3BP). This protein is essential in forming the multiunit structure of PDC. Another moonlighting activity of DLDH, which is described in this Review, is its DNA-binding capacity that may affect DNA chelation and shredding leading to apoptotic processes in living cells. The typical ROS-generation by DLDH, which occurs in association with its enzymatic activity and its implications in cancer and apoptotic cell death are also discussed.

show abstract

Section: Dldh Rgd As a Molecular Bridge Between Tio 2 -Based Medical Implants And Bone Forming Cells For Osseointegration Enhancementmentioning

confidence: 99%

mentioning

confidence: 99%

The moonlighting activities of dihydrolipoamide dehydrogenase: Biotechnological and biomedical applications

Fleminger

Dayan

2021

J of Molecular Recognition

Self Cite

View full text Add to dashboard Cite

show abstract

“…CHED motifs are known to coordinately bind metal ions but how this motif coordinates to the Ti in TiO 2 is not yet known [60]. Very recently, hDLDH was coated onto the TiO 2 surface layer of a Ti-containing implant to enhance the osseointegration property of the implant [61]. The use of a coating of a human protein is expected to enhance the biocompatibility of the implant surface.…”

Section: The Biological Use and Solubility Of Tio2 And Its Npsmentioning

confidence: 99%

Fueling a Hot Debate on the Application of TiO2 Nanoparticles in Sunscreen

Sharma

Gaur

et al. 2019

Materials

View full text Add to dashboard Cite

Titanium is one of the most abundant elements in the earth’s crust and while there are many examples of its bioactive properties and use by living organisms, there are few studies that have probed its biochemical reactivity in physiological environments. In the cosmetic industry, TiO2 nanoparticles are widely used. They are often incorporated in sunscreens as inorganic physical sun blockers, taking advantage of their semiconducting property, which facilitates absorbing ultraviolet (UV) radiation. Sunscreens are formulated to protect human skin from the redox activity of the TiO2 nanoparticles (NPs) and are mass-marketed as safe for people and the environment. By closely examining the biological use of TiO2 and the influence of biomolecules on its stability and solubility, we reassess the reactivity of the material in the presence and absence of UV energy. We also consider the alarming impact that TiO2 NP seepage into bodies of water can cause to the environment and aquatic life, and the effect that it can have on human skin and health, in general, especially if it penetrates into the human body and the bloodstream.

show abstract

“…Studies investigating the efficacy of titanium as an implant material have comprised in vitro experiments examining protein adsorption ability, cell induction ability, cell adhesion ability, cell proliferative ability, and calcification ability etc. on titanium [10][11][12][13][14][15][16] . Meanwhile, in vivo experiments have involved studies of bone tissue formation around the titanium after the implantation of titanium in experiments using animals, such as rats or rabbits [17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

A Study of Bone Formation around Titanium Implants Using Frozen Sections

Kawamoto

Suzuki

Nagano

et al. 2021

J. hard tissue biol.

View full text Add to dashboard Cite

Titanium is most widely used for implants. Almost all the histological studies of the implants have been carried out with polished specimens and the use of frozen sections are challenging. This study focused to define the formation process of bone around titanium with frozen sections made from tissue implanted with a commercially pure titanium foil (Tifoil). We inserted the Ti-foil with a 30-μm thickness into rat femurs and extracted it after 1, 3, 5, 7, 10, 15, and 30 days. After freezing, they were sliced into 3-μm thick serial frozen sections and the sections were used for hematoxylin and eosin (H&E) staining, Masson trichrome staining, Alizarin Red S staining, enzymatic staining (ALPase and TRAPase), immunostaining (osteopontin, osteocalcin, and collagen type I), and elemental analysis. At 1 day after the implantation, the area around the Ti-foil was filled with blood and there are no collagen fibers and no proliferated cells in the area. At 3 days, the new collagen fibers were observed on the marrow side of the blood clot. The proliferated cells were observed around the fibers and they were positive for immunostaining to osteopontin, osteocalcin, and collagen type I. After 5 days, calcium precipitation was observed on the newly formed collagen fibers. After 7 days, the calcification progressed and started to reach the Ti-foil surface. After 10 days, calcification progressed to the area around the Ti-foil. At 15 days, a remarkable bone resorption appears on the marrow side. At 30 days, further resorption was observed and bony tissue was seen on the Ti-foil surface only. These results clearly showed that the bone around the Ti-foil is formed after undergoing the blood clotting process around the Ti-foil, osteoblast and fibroblast proliferation, calcium precipitation on the collagen fibers, bone formation around the Ti-foil, and bone resorption by osteoclasts.

show abstract

RGD‐modified dihydrolipoamide dehydrogenase as a molecular bridge for enhancing the adhesion of bone forming cells to titanium dioxide implant surfaces

Cited by 11 publications

References 48 publications

The moonlighting activities of dihydrolipoamide dehydrogenase: Biotechnological and biomedical applications

The moonlighting activities of dihydrolipoamide dehydrogenase: Biotechnological and biomedical applications

Fueling a Hot Debate on the Application of TiO2 Nanoparticles in Sunscreen

A Study of Bone Formation around Titanium Implants Using Frozen Sections

Contact Info

Product

Resources

About