TGF beta receptor II interacting protein-1, an intracellular protein has an extracellular role as a modulator of matrix mineralization

Ramachandran, Aparna; Ravindran, Sriram; Huang, Chun Chieh; George, Anne

doi:10.1038/srep37885

Cited by 29 publications

(30 citation statements)

References 38 publications

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“…Stable overexpression was performed by transfecting the pECFP vector (Clontech Laboratories, Mountain View, CA, United States) containing the rat TRIP-1 cDNA in MC3T3-E1 cells as published earlier ( Ramachandran et al, 2016 ). Cells mock transfected with the empty vector served as the control.…”

Section: Methodsmentioning

confidence: 99%

“…Twenty microliters of the resuspended exosomes were added to 300 mesh formvar coated nickel grids and viewed without coating. For immunogold cytochemistry, published protocols were followed ( Ramachandran et al, 2016 ). Briefly, the grids were fixed in 10% neutral formalin, permeabilized with PBS containing 1% Trton-X100 for 30 min and blocked with 3% BSA for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, its localization in the primary spongiosa suggests that TRIP-1 might function in the extracellular matrix to regulate mineralization as well as promote angiogenesis. A pivotal role for TRIP-1 in mineralization has been recently demonstrated in an in vitro nucleation model ( Ramachandran et al, 2016 , 2018 ).…”

Section: Introductionmentioning

confidence: 93%

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TRIP-1 Promotes the Assembly of an ECM That Contains Extracellular Vesicles and Factors That Modulate Angiogenesis

Chen

George

2018

Front. Physiol.

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Transforming growth factor beta receptor II interacting protein-1 (TRIP-1) was recently localized in the mineralized matrices of bone and dentin. The function of TRIP-1 in the ECM is enigmatic, as it is known to function as an intracellular endoplasmic reticulum protein during protein synthesis. Based on its localization pattern in bones and teeth, we posited that TRIP-1 must function as a regulatory protein with multiple functions during mineralization. In this study, we determined the in vivo function of TRIP-1 by an implantation assay performed using recombinant TRIP-1 and TRIP-1 overexpressing and knocked down cells embedded in a 3D biomimetic scaffold. After 4 weeks, the subcutaneous tissues from TRIP-1 overexpressing cells and scaffolds containing recombinant TRIP-1 showed higher expression levels of several ECM proteins such as fibronectin and collagen I. Picrosirius red and polarized microscopy was used to identify the birefringence of the collagen fibrils in the extracellular matrix (ECM). Interestingly, knockdown of TRIP-1 resulted in lower fibronectin and downregulation of the activation of the ERK MAP kinase. We further demonstrate that TRIP-1 overexpression leads to higher expression of pro-angiogenic marker VEGF and downregulation of anti-angiogenic factors such as pigment epithelium-derived factor and thrombospondin. Field emission scanning electron microscope results demonstrated that TRIP-1 overexpressing cells released large amount of extracellular microvesicles which were localized on the fibrillar matrix in the ECM. Overall, this study demonstrates that TRIP-1 can promote secretion of extracellular vesicles, synthesis of key osteogenic ECM matrix proteins and promote angiogenesis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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TRIP-1 Promotes the Assembly of an ECM That Contains Extracellular Vesicles and Factors That Modulate Angiogenesis

Chen

George

2018

Front. Physiol.

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“…It supports intrinsic structural flexibility to accommodate interactions in enamel biomineralization. Transforming growth factor beta receptor II interacting protein 1 (TRIP-1) is an intracellular protein that participates in matrix mineralization [17]. It is localized in the ECM of bone.…”

Section: Introductionmentioning

confidence: 99%

Role of Calcium Bio-Minerals in Regenerative Medicine and Tissue Engineering

Upadhyay¹

2017

JSRT

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Present review article emphasize role of biominerals in regenerative medicine and tissue engineering. Among all biominerals calcium is essential for body growth and development. It also performs many fundamental functions in cellular metabolism. Inside cell organic matrix is calcified by calcium phosphate minerals. It also embeds bone cells which participate in the maintenance and organization of bone. This article also emphasizes use of hydroxyapatite a natural mineral used as a bone-building supplement with superior absorption in comparison to calcium. It also explains use of scaffolds that mimic the structure and composition of bone tissue and cells. It also signifies use of HAc microparticles or microparticles loaded with PL, superparamagnetic iron oxide nanoparticles, composite scaffolds of nano-hydroxyapatite (nHAp) and silk fibroin (SF) in bone regeneration mainly in osteoregenerative therapy. For better and successful bone regeneration there is a need to develop low cost sintered hydroxyfluorapatite discs to support cellular proliferation and colonization, tailored mineralization, cell and drug delivery. All adhesion components should show low immunoreactivity and high biocompatibility with natural bone tissues. There is an essential need to make new biocompatible materials for scaffolding, biomeinerals and cementing formulations for regeneration of bones, craniomaxillofacial, dental and orthopedic surgery.

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“…In addition, exosomes from osteoblast carry transforming growth factor beta receptor II interacting protein1 (TRIP-1), a regulator of osteoblast function. TRIP-1 from the exosomes can bind to type I collagen and promote its mineralized extracellular matrix, therefore bone mineralizing [108]. Sema4D is an osteoclast membrane protein that can be carried in exosomes derived from osteoclasts and acts on the receptor Plexin B on osteoblasts [81].…”

Section: Key Protein Factors Carried By Exosomes Regulate Bone Regenementioning

confidence: 99%

Potential Therapeutic Applications of Exosomes in Bone Regenerative Medicine

Yang¹,

Zhu²,

Lu³

et al. 2019

Osteogenesis and Bone Regeneration

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The ability of bone regeneration is relatively robust, which is crucial for fracture healing, but delayed healing and nonunion are still common problems in clinical practice. Fortunately, exciting results have been achieved for regenerative medicine in recent years, especially in the area of stem cell-based treatment, but all these cell-based approaches face challenging problems, including immune rejection. For this reason, exosomes, stem cell-derived small vesicles of endocytic origin, have attracted the attention of many investigators in the field of bone regeneration. One of the attractive features of exosomes is that they are small and can travel between cells and deliver bioactive products, including miRNA, mRNA, proteins, and various other factors, to promote bone regeneration, with undetectable immune rejection. In this chapter, we intend to briefly update the recent progressions, and discuss the potential challenges in the target areas. Hopefully, our discussion would be helpful not only for the clinicians and the researchers in the specific disciplines but also for the general audiences as well.

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TGF beta receptor II interacting protein-1, an intracellular protein has an extracellular role as a modulator of matrix mineralization

Cited by 29 publications

References 38 publications

TRIP-1 Promotes the Assembly of an ECM That Contains Extracellular Vesicles and Factors That Modulate Angiogenesis

TRIP-1 Promotes the Assembly of an ECM That Contains Extracellular Vesicles and Factors That Modulate Angiogenesis

Role of Calcium Bio-Minerals in Regenerative Medicine and Tissue Engineering

Potential Therapeutic Applications of Exosomes in Bone Regenerative Medicine

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