Transport and binding of insulin-like growth factor I through articular cartilage

Garcia, A.Minerva; Szász, Nóra; Trippel, Stephen B.; Morales, Teresa I.; Grodzinsky, Alan J.; Frank, Eliot H.

doi:10.1016/s0003-9861(03)00215-7

Cited by 59 publications

(63 citation statements)

References 39 publications

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“…It also plays an important role in stimulating collagen and proteoglycan synthesis in cartilage through an autocrine feedback mechanism [25]. Since hIGF-1 is a major chondro-enhancing agent, notwithstanding its attenuated effect on aged cartilage, it would appear a logical choice for gene therapy approaches [4,5,7,12,16]. It is a relatively small gene of approximately 45 kb pairs with the transcribed region spanning less than 1 kb, and the DNA sequence is known in most species.…”

Section: Discussionmentioning

confidence: 99%

Treating Human Meniscal Fibrochondrocytes with hIGF-1 Gene by Liposome

Zhang

Leng

Wang

et al. 2009

Clin Orthop Relat Res

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The menisci are intraarticular fibrocartilaginous structures essential to the normal function of the knee that lack the ability to self-repair. Human meniscal fibrochondrocytes may respond to beneficial genes like human insulin growth factor-1 (hIGF-1) and the meniscal cell may be a feasible donor for gene therapy. To explore this possibility, we amplified the hIGF-1 gene sequence in full length and cloned it into a bicistronic plasmid. This gene was then transfected into cultured human meniscal fibrochondrocytes by the liposome FuGene 6. Green fluorescence was expressed in part of the cells 6 hours after transfection and increased gradually, with a peak concentration of the hIGF-1 in the supernatants to 22.68 ng/mL 56 hours after transfection. Phenotypes of some cells changed and the proliferation accelerated after transfection. Flow cytometry analysis demonstrated upregulation of cell numbers in the G2 and S stages after hIGF-1 gene introduction. We conclude the hIGF-1 gene can be transfected into the human meniscal cell efficiently by liposome and it causes accelerated proliferation and differentiation. Within 10 days after transfection, the cytokine appears to be secreted into supernatants with the bioactivity and promotes the proliferation of the NIH 3T3 cell line.

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Section: Discussionmentioning

confidence: 99%

Treating Human Meniscal Fibrochondrocytes with hIGF-1 Gene by Liposome

Zhang

Leng

Wang

et al. 2009

Clin Orthop Relat Res

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“…Diffusion data were fit to a curve of the form A·[1 2 exp (2t/t)], where A is maximum percentage CT attenuation, t is diffusion time, and the t value was calculated as the time required to reach 63.2% of the maximum CT attenuation (9). Relative uptake data were fit with a linear curve for ioxaglate and a Langmuir isotherm of the form (A·x)/(x + b), where A is the maximum contrast agent concentration in the cartilage, x is contrast agent reservoir concentration, and b is the reservoir concentration at which the cartilage internal concentration is at 50% of its maximum value (or EC 50 ), for CA 4+ (23). Student t tests were used to compare GAG contents and diffusion time constants (SPSS, version 17.0; SPSS, Chicago, Ill).…”

Section: Computational and Statistical Methodsmentioning

confidence: 99%

“…If the affinity is sufficiently strong because of a collection of electrostatic and other noncovalent interactions, there is the additional possibility of binding between the contrast agent and the GAGs. For example, previous studies with singly charged ions (Na + ) and cartilage explants have shown that the interaction with GAGs can be described by Donnan partitioning (24,25), whereas the binding of multicharged peptides to GAG can be governed by binding and/or Donnan partitioning, depending on the specific composition being investigated (23,26,27). Mechanistic studies, including competitive binding experiments, are planned by the 4+ at 12 mg I/mL, B, ioxaglate at 12 mg I/mL, and, C, ioxaglate at 80 mg I/mL.…”

Section: Experimental Studies: Ct Enhanced With High-affinity Cationimentioning

confidence: 99%

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

Stewart

Bansal²,

Entezari³

et al. 2013

Radiology

104

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Purpose:To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA 4+ ) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA 4+ and ioxaglate in a rabbit model. Materials and Methods:All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA 4+ to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (t) were compared by using a Student t test. Results:The uptake of CA 4+ in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material-enhanced cartilage reached a steady CT attenuation for both CA 4+ and ioxaglate, with t values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA 4+ (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). Conclusion:The affinity of the cationic contrast agent CA 4+ to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage.q RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup /suppl

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“…[1][2][3] Studies of bovine cartilage explant cultures indicate that resident IGFBPs slow down transport of the IGF ligands through the tissue. 4,5 This effect of the IGFBPs can be ameliorated by increased fluid flow, such as occurs during mechanical compression of the tissue. 5 These transport studies suggested that IGFBPs may restrict ligand access to cellular receptors.…”

mentioning

confidence: 99%

“…4,5 This effect of the IGFBPs can be ameliorated by increased fluid flow, such as occurs during mechanical compression of the tissue. 5 These transport studies suggested that IGFBPs may restrict ligand access to cellular receptors. Recent studies used mutated analogs of IGFs with low affinity for the binding proteins and confirmed that IGFBPs in normal and OA cartilages can contribute to the regulation of the anabolic IGF signal.…”

mentioning

confidence: 99%

Subcellular distribution of the insulin‐like growth factor (IGF) binding proteins (IGFBPs) 2 and 3 in articular chondrocytes

Sun

Hunziker

Morales

2008

Journal Orthopaedic Research

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The insulin-like growth factor (IGF) is a major anabolic regulator in articular cartilage. The IGF-binding proteins (IGFBPs) are increased during osteoarthritis (OA), but the function of the later proteins remains unknown. In general, the IGFBPs are pluripotential effectors capable of IGF regulation and of acting on their own to control key cell functions, including survival and proliferation. The independent functions are often associated with their cell location, and therefore this study explores the distribution of IGFBP-2 and IGFBP-3 in articular chondrocytes. Immunohistochemistry was used to localize IGFBP-2 in normal human articular cartilage. Bovine chondrocytes were used for subcellular fractionation (hypotonic cell lysis) under nonreducing conditions and nuclear purification (centrifugation on sucrose cushions). Cell fraction markers and IGFBPs were assayed in the subcellular fractions by Western immunoblot. The IHC results showed association of IGFBP-2 with chondrocytes, but not with the nuclei. Subcellular fractionation of isolated chondrocytes yielded intact nuclei as assessed at the light microscopic level; the nuclear marker histone H1 was exclusively associated with this fraction. More than 90% of the cytoplasmic marker GAPDH and all the detectable IGFBP-2 were in the cytoplasmic fraction. Immunoreactive IGFBP-3 was found in the cytoplasmic and peri-nuclear/nuclear fractions. Chondrocytes contain intracellular IGFBP-2 and IGFBP-3 but only IGFBP-3 is associated with nuclei. This suggests the hypothesis that the actions of these IGFBPs in articular cartilage extend beyond the classic modulation of IGF receptor action. ß

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Transport and binding of insulin-like growth factor I through articular cartilage

Cited by 59 publications

References 39 publications

Treating Human Meniscal Fibrochondrocytes with hIGF-1 Gene by Liposome

Treating Human Meniscal Fibrochondrocytes with hIGF-1 Gene by Liposome

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

Subcellular distribution of the insulin‐like growth factor (IGF) binding proteins (IGFBPs) 2 and 3 in articular chondrocytes

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