VEGF: an Essential Mediator of Both Angiogenesis and Endochondral Ossification

Dai, Jing; Rabie, A. Bakr M.

doi:10.1177/154405910708601006

Cited by 334 publications

(280 citation statements)

References 170 publications

(190 reference statements)

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“…Although dynamic culture conditions likely enhanced nutrient transport within the pore layer [5], it is possible that cells on the surface of the porous layer caused more hypoxic conditions for the cells residing within the deeper pores. Although our previous data suggest that nutrient diffusion is not a limitation in vivo, where blood vessels are able to perfuse the pore network and allow bone to penetrate the full depth of the pore layer [10], hypoxia is known to influence osteoblast differentiation and endochondral ossification [8,43]. This hypothesis is supported by the increased VEGF production of MC3T3 cells on PEEK-SP groups (Fig.…”

Section: Discussionmentioning

confidence: 77%

Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

Torstrick

Evans

Stevens

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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Background Despite its widespread use in orthopaedic implants such as soft tissue fasteners and spinal intervertebral implants, polyetheretherketone (PEEK) often suffers from poor osseointegration. Introducing porosity can overcome this limitation by encouraging bone ingrowth; however, the corresponding decrease in implant strength can potentially reduce the implant's ability to bear physiologic loads. We have previously shown, using a single pore size, that limiting porosity to the surface of PEEK implants preserves strength while supporting in vivo osseointegration. However, additional work is needed to investigate the effect of pore size on both the mechanical properties and cellular response to PEEK. Questions/purposes (1) Can surface porous PEEK (PEEK-SP) microstructure be reliably controlled? (2) What is the effect of pore size on the mechanical properties of PEEK-SP? (3) Do surface porosity and pore size influence the cellular response to PEEK? Methods PEEK-SP was created by extruding PEEK through NaCl crystals of three controlled ranges: 200 to 312, 312 to 425, and 425 to 508 lm. Micro-CT was used to characterize the microstructure of PEEK-SP. Tensile, fatigue, and interfacial shear tests were performed to compare the mechanical properties of PEEK-SP with injectionmolded PEEK (PEEK-IM). The cellular response to PEEK-SP, assessed by proliferation, alkaline phosphatase activity, vascular endothelial growth factor production, and calcium content of osteoblast, mesenchymal stem cell, and preosteoblast (MC3T3-E1) cultures, was compared with that of machined smooth PEEK and Ti6Al4V. Results Micro-CT analysis showed that PEEK-SP layers possessed pores that were 284 ± 35 lm, 341 ± 49 lm, and 416 ± 54 lm for each pore size group. Porosity and

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Section: Discussionmentioning

confidence: 77%

Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

Torstrick

Evans

Stevens

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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“…Because endochondral ossification is orchestrated by the dynamic interaction of cartilage development and angiogenesis, (1,2) we examined a role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating TG mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Expression patterns of Dkk1 and Dkk2 are opposite during in vitro chondrogenesis and hypertrophic maturation of chondrocyte: downregulation of Dkk1 and upregulation of Dkk2.…”

Section: Discussionmentioning

confidence: 99%

“…Endochondral ossification is orchestrated by the dynamic interaction of cartilage development and angiogenesis. (1,2) Proliferative chondrocytes in the growth plate stop proliferating and maturate into hypertrophic chondrocytes, which in turn undergo apoptosis followed by blood vessel invasion. Resorption of the hypertrophic cartilage by chondroclasts and osteoclasts leads to the deposition of bone matrix.…”

Section: Introductionmentioning

confidence: 99%

“…Resorption of the hypertrophic cartilage by chondroclasts and osteoclasts leads to the deposition of bone matrix. (1,2) Blood vessel invasion from the metaphysis into avascular cartilage is coupled to chondrocyte hypertrophy. Hypertrophic chondrocytes secrete vascular endothelial growth factor (VEGF), which is required for cartilage vascularization.…”

Section: Introductionmentioning

confidence: 99%

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Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Oh¹,

Ryu²,

Jeon³

et al. 2012

Journal of Bone and Mineral Research

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Developing cartilage serves as a template for long-bone development during endochondral ossification. Although the coupling of cartilage and bone development with angiogenesis is an important regulatory step for endochondral ossification, the molecular mechanisms are poorly understood. One possible mechanism involves the action of Dickkopf (DKK), which is a family of soluble canonical Wnt antagonists with four members (DKK1-4). We initially observed opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite specific expression pattern during cartilage development, chondrocyte-and hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal developmental phenotypes. However, Dkk1 misexpression in endothelial cells resulted in defects of endochondral ossification and reduced skeletal size. The defects are caused by the inhibition of angiogenesis in developing bone and subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage resorption. ß

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“…VEGF-A121 is the only other of the six VEGF-A isoforms that has been reported in cardiac gene therapy studies. However, VEGF-A121 has been reported to have 10 to 100 times lower endothelial cell mitogenic activity than VEGF-A165 [84], so comparing studies with genes encoding different isoforms is difficult. VEGF-2 (also know as VEGF-C) [85] and VEGF-D [86] have also been used.…”

Section: Vegf Isoformsmentioning

confidence: 99%

Non‐viral gene therapy for myocardial engineering

Holladay

O’Brien

Pandit

2010

WIREs Nanomed Nanobiotechnol

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Despite significant advances in surgical and pharmacological techniques, myocardial infarction remains the main cause of morbidity in the developed world because no remedy has been found for the regeneration of infarcted myocardium. Once the blood supply to the area in question is interrupted, the inflammatory cascade, among other mechanisms, results in the damaged tissue becoming a scar. The goals of cardiac gene therapy are essentially to minimize damage, to promote regeneration or some combination thereof. While the vector is, in theory, less important than the gene being delivered, the choice of vector can have a significant impact. Viral therapies can have very high transfection efficiencies, but disadvantages include immunogenicity, retroviralmediated insertional mutagenesis and the expense and difficulty of manufacture. For these reasons, researchers have focused on non-viral gene therapy as an alternative. In this review, naked plasmid delivery, or the delivery of complexed plasmids, and cellmediated gene delivery to the myocardium will be reviewed. Pre-clinical and clinical trials in the cardiac tissue will form the core of the discussion. While unmodified stem cells are sometimes considered therapeutic vectors based on paracrine mechanisms of action basic understanding is limited. Thus, only genetically modified cells will be discussed as cell-mediated gene therapy.Ischemic heart disease, which includes acute damage due to myocardial infarction (MI) and chronic damage due to atherosclerotic narrowing of vessels, accounts for 35% of deaths reported in the United States every year [1]. MI, which is literally the death of cardiac tissue due to lack of 2 oxygen supply, is the result of the occlusion of a coronary artery. Within a few hours of interrupted blood supply, affected cardiomyocytes die. While the body has adaptive mechanisms, such as hypertrophy of the undamaged cardiac muscle and the development of collateral blood supply to minimize the damage, ischemic heart disease remains the most common cause of death in developed countries [2].The delivery of plasmid DNA to the myocardium is a complicated problem as the transfection efficiency of unmodified DNA is quite low, but complexation with agents designed to improve transfection can increase the cytotoxicity of the treatment [3]. Delivery of uncomplexed plasmid DNA is conceptually the simplest gene delivery technique, but these plasmids have extremely low transfection efficiencies in vitro and are not particularly effective in vivo. Compared to viral vectors, transgene expression is almost negligible and the expression time is also very limited [4]. However, there are significant advantages in using plasmids instead of viruses, such as ease of preparation (large and small scale), very low immunogenicity (as there are essentially no protein or membrane components in the plasmid), capacity for long term storage, ease of recombinant manipulation and much larger expression cassettes [4]. A variety of non-viral techniques are available to improve...

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VEGF: an Essential Mediator of Both Angiogenesis and Endochondral Ossification

Cited by 334 publications

References 170 publications

Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Non‐viral gene therapy for myocardial engineering

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