Transport of Insulin-Like Growth Factor 1 in Intervertebral Disc: Effect of Binding Interactions and Inhomogeneous Distribution of Binding Proteins in Annulus Fibrosus and Nucleus Pulposus

2010 ◽  
Author(s):  
Francesco Travascio ◽  
Chun Yuh Huang ◽  
Wei Yong Gu
Keyword(s):  
Growth Factor ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Reactive Transport ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Binding Interactions

The intervertebral disc (IVD), being the largest avascular structure in human body, receives nourishment from the vascular network present near its periannular surface and at cartilage endplates (CEPs). It is believed that insufficient nutritional supply is a major cause for disc degeneration [1]. Understanding the mechanisms of solute transport in IVD is crucial for elucidating the etiology of disc degeneration, and to develop strategies for tissue repair (in vivo), and tissue engineering (in vitro). Transport in IVD is complex and involves a series of electromechanical, chemical, and biological coupled events. This study focused on the implications of solute-tissue reversible binding reactions on transport phenomena in the disc. A two dimensional (2D) finite element model was developed to predict diffusive-reactive transport in IVD. The numerical model was used to simulate transport of insulin-like growth factor 1 (IGF-1) in IVD, in the presence of binding interactions between IGF-1 and IGF-binding proteins (IGFBP-3) located on the extracellular matrix (ECM) of the disc.

scholarly journals Separation of Fast from Slow Anabolism by Site-specific PEGylation of Insulin-like Growth Factor I (IGF-I)

2011 ◽  
Vol 286 (22) ◽  
pp. 19501-19510 ◽  
Author(s):  
Friedrich Metzger ◽  
Waseem Sajid ◽  
Stefanie Saenger ◽  
Christian Staudenmaier ◽  
Chris van der Poel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Site Specific ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) has important anabolic and homeostatic functions in tissues like skeletal muscle, and a decline in circulating levels is linked with catabolic conditions. Whereas IGF-I therapies for musculoskeletal disorders have been postulated, dosing issues and disruptions of the homeostasis have so far precluded clinical application. We have developed a novel IGF-I variant by site-specific addition of polyethylene glycol (PEG) to lysine 68 (PEG-IGF-I). In vitro, this modification decreased the affinity for the IGF-I and insulin receptors, presumably through decreased association rates, and slowed down the association to IGF-I-binding proteins, selectively limiting fast but maintaining sustained anabolic activity. Desirable in vivo effects of PEG-IGF-I included increased half-life and recruitment of IGF-binding proteins, thereby reducing risk of hypoglycemia. PEG-IGF-I was equipotent to IGF-I in ameliorating contraction-induced muscle injury in vivo without affecting muscle metabolism as IGF-I did. The data provide an important step in understanding the differences of IGF-I and insulin receptor contribution to the in vivo activity of IGF-I. In addition, PEG-IGF-I presents an innovative concept for IGF-I therapy in diseases with indicated muscle dysfunction.

Production of insulin-like growth factor I (IGF-I) and IGF-binding proteins by rat intestinal stromal cells in vitro

1998 ◽  
Vol 54 (2) ◽  
pp. 158-166
Author(s):  
R. G. MacDonald ◽  
R. H. McCusker ◽  
D. J. Blackwood ◽  
J. A. Vanderhoof ◽  
J. H. Y. Park
Keyword(s):  
Growth Factor ◽  
Stromal Cells ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Growth Factor I

Increased secretion of insulin-like growth factor-binding proteins and decreased secretion of insulin-like growth factor-II by muscle from growth-retarded neonatal rats

1991 ◽  
Vol 130 (1) ◽  
pp. 33-42 ◽  
Author(s):  
R. J. Frampton ◽  
H. A. Jonas ◽  
R. G. Larkins
Keyword(s):  
Growth Factor ◽  
Conditioned Medium ◽  
Binding Proteins ◽  
Muscle Protein ◽  
Growth Potential ◽  
Insulin Like Growth Factor ◽  
Neonatal Rats ◽  
Igf Binding Proteins ◽  
Igf I

ABSTRACT Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) may be important factors in the control of neonatal growth. We have examined the production, in vitro, of IGFBPs and IGFs by hindlimb skeletal muscle from normal and small-for-gestational age (SGA) neonatal rats. Conditioned medium was collected from muscle strips after incubation at 37 °C for 2 h in Ham's F-12 medium. The conditioned medium was subjected to acid-gel permeation chromatography to separate IGFBPs from IGFs. The binding of 125I-labelled IGF-I to IGFBPs from both control and SGA muscle was displaced equipotently by IGF-I and IGF-II and not at all by insulin. IGFBPs from control and SGA muscles bound IGF-I with comparable affinities (Kd = 0·071 and 0·069 nmol/l respectively). When IGF-II was used as tracer, neither IGF-I nor insulin competed for binding. Western ligand blots of IGFBPs in conditioned media from both control and SGA muscles showed three bands of radioactivity at molecular masses equivalent to 24, 30 and 40 kDa. When the release of IGFBPs by muscle tissue in vitro was quantified by measuring the number of IGF-I binding sites in acid-fractionated medium it was apparent that the muscles from SGA pups secreted significantly more IGFBPs (39·3±7·5 fmol/mg muscle protein per 2 h) than the muscles from control pups (17·8±2·7 fmol/mg protein per 2 h; P < 0·05). In contrast to the IGFBPs, more IGF activity was secreted by the muscles from the control pups (61·1±15·6 fmol/mg muscle protein per 2 h) than the muscles from the SGA pups (12·6±5·8 fmol/mg muscle protein per 2 h; P < 0·05). Analysis of the IGF activity with assays specific for IGF-I and IGF-II showed that both SGA and control muscles secreted predominantly IGF-II with approximately 10% of the total IGF activity measurable as IGF-I. This differential secretion of IGFBPs and IGFs may be associated with the reduced growth potential of the SGA neonate. Journal of Endocrinology (1991) 130, 33–42

scholarly journals Platelet-Derived Biomaterials Exert Chondroprotective and Chondroregenerative Effects on Diabetes Mellitus-Induced Intervertebral Disc Degeneration

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1054
Author(s):  
Wen-Cheng Lo ◽  
Chun-Chao Chang ◽  
Chun-Hao Chan ◽  
Abhinay Kumar Singh ◽  
Yue-Hua Deng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Transforming Growth Factor ◽  
Disc Height ◽  
Therapeutic Effects

Complications of diabetes mellitus (DM) range from acute to chronic conditions, leading to multiorgan disorders such as nephropathy, retinopathy, and neuropathy. However, little is known about the influence of DM on intervertebral disc degeneration (IVDD). Moreover, traditional surgical outcomes in DM patients have been found poor, and to date, no definitive alternative treatment exists for DM-induced IVDD. Recently, among various novel approaches in regenerative medicine, the concentrated platelet-derived biomaterials (PDB), which is comprised of transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), etc., have been reported as safe, biocompatible, and efficacious alternatives for various disorders. Therefore, we initially investigated the correlations between DM and IVDD, through establishing in vitro and in vivo DM models, and further evaluated the therapeutic effects of PDB in this comorbid pathology. In vitro model was established by culturing immortalized human nucleus pulposus cells (ihNPs) in high-glucose medium, whereas in vivo DM model was developed by administering streptozotocin, nicotinamide and high-fat diet to the mice. Our results revealed that DM deteriorates both ihNPs and IVD tissues, by elevating reactive oxygen species (ROS)-induced oxidative stress, inhibiting chondrogenic markers and disc height. Contrarily, PDB ameliorated IVDD by restoring cellular growth, chondrogenic markers and disc height, possibly through suppressing ROS levels. These data imply that PDB may serve as a potential chondroprotective and chondroregenerative candidate for DM-induced IVDD.

scholarly journals Adjunctive Growth Hormone during Ovarian Hyperstimulation Increases Levels of Insulin-Like Growth Factor Binding Proteins in Follicular Fluid: A Randomized, Placebo-Controlled, Cross-Over Study*

1997 ◽  
Vol 82 (4) ◽  
pp. 1171-1176
Author(s):  
Jaron Rabinovici ◽  
Nicholas A. Cataldo ◽  
Pramila Dandekar ◽  
Stephen M. Rosenthal ◽  
Sharron E. Gargosky ◽  
...  
Keyword(s):  
Growth Factor ◽  
Follicular Fluid ◽  
Binding Proteins ◽  
Serum Levels ◽  
Insulin Like Growth Factor ◽  
Double Blind ◽  
Igf Binding Proteins ◽  
Vitro Fertilization ◽  
Igf I

Abstract GH increases circulating insulin-like growth factor I (IGF-I), which can promote the growth and differentiated function of ovarian granulosa and theca cells. Reported studies of GH as an adjunct to menotropin stimulation in women, largely those with ovarian dysfunction, have not consistently shown a benefit of GH, despite increases in serum and follicular fluid IGF-I. We hypothesized that changes in intrafollicular IGF-binding proteins (IGFBPs), which can antagonize IGF actions on granulosa cells, may underlie the inconsistent effects of GH. In the present study of GH, administered in double-blind, placebo-controlled, cross-over fashion to regularly cycling women undergoing in vitro fertilization, we found that follicular fluid levels of IGFBP-1, -3, and -4 and serum levels of IGFBP-3, as well as follicular fluid and serum IGF-I, were significantly increased in the GH-treated cycles, when compared with the placebo cycle of the same patient. We suggest that the net increase in intrafollicular IGFBPs in GH cycles may mitigate the potential beneficial effect of increased IGF-I.

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