The Insulin-like Growth Factors (IGFs) I and II Bind to Articular Cartilage via the IGF-binding Proteins

Bhakta, Nirav R.; Garcia, A.Minerva; Frank, Eliot H.; Grodzinsky, Alan J.; Morales, Teresa I.

doi:10.1074/jbc.275.8.5860

Cited by 60 publications

(48 citation statements)

References 30 publications

(27 reference statements)

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“…Although the IGF-I assay disassociates most binding proteins present in the synovial fluid, providing an accurate measure of total IGF-I, previous work suggests that IGF-I ligand bound to IGF-I binding proteins may be degraded more slowly over time or internalized in chondrocytes. 34 Furthermore, IGF-I actively enters the circulation in the live animal, particularly the unbound ligand, which may further reduce IGF-I levels in synovial fluid compared to culture medium.…”

Section: Resultsmentioning

confidence: 99%

Direct adenovirus-mediated IGF-I gene transduction of synovium induces persisting synovial fluid IGF-I ligand elevations

et al. 2006

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Section: Resultsmentioning

confidence: 99%

Direct adenovirus-mediated IGF-I gene transduction of synovium induces persisting synovial fluid IGF-I ligand elevations

et al. 2006

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“…Change in pressure and shear stresses that are induced by joint movement may cause deformation of the extracellular matrix, thus changing the osmolarity, ionic concentration, and pH of the cellular environment. [20][21][22] Some biochemical changes may mediate the process. We are now evaluating how the mechanical information was translated into chemical and/or biological information by using in vitro mechanical environments.…”

Section: Discussionmentioning

confidence: 99%

In vivo mechanical condition plays an important role for appearance of cartilage tissue in ES cell transplanted joint

Nakajima

Wakitani

Harada

et al. 2007

Journal Orthopaedic Research

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The objective of this study was to evaluate the effects of the mechanical environment on the formation of cartilage tissue in transplanted embryonic stem (ES) cells. Full-thickness osteochondral defects were created on the patella groove of SD rats, and ES cells (CCE ES cells obtained from 129/Sv/Ev mice and Green ES FM260 ES cells obtained from 129SV [D3] -Tg [NCAG-EGFP] CZ-001-FM260Osb mice) were transplanted into the defects embedded in collagen gel. The animals were randomly divided into either the joint-free group (JF group) or the joint-immobilized group (JI group) for 3 weeks after a week postoperatively. The results showed that cartilage-like tissue formed in the defects of the JF group whereas large teratomatous masses developed in the defects of the JI group. Some parts of the cartilage-like tissue and the teratomatous masses were positively stained with immunostain for GFP when the Green ES FM260 ES cells were transplanted. It is suggested that the environment plays an important role for ES cells in the process of repairing cartilage tissue in vivo. ß

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“…7,8 It has been proposed that matrix-associated IGFBPs control IGF-I action by slowing down their transport to the cells. 4 The objective of the present study was to gain further insight into their range of action by rigorously defining and comparing their site(s) of cellular residence using IHC and subcellular fractionation and nuclear purification techniques. The results show that IGFBP-2 and IGFBP-3 are associated with intracellular fractions in chondrocytes, but their distribution pattern is distinct: IGFBP-2 was exclusively detected in the cytoplasm, while the perinuclear/nuclear fraction contained IGFBP-3.…”

Section: Discussionmentioning

confidence: 99%

“…[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%

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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The Insulin-like Growth Factors (IGFs) I and II Bind to Articular Cartilage via the IGF-binding Proteins

Cited by 60 publications

References 30 publications

Direct adenovirus-mediated IGF-I gene transduction of synovium induces persisting synovial fluid IGF-I ligand elevations

Direct adenovirus-mediated IGF-I gene transduction of synovium induces persisting synovial fluid IGF-I ligand elevations

In vivo mechanical condition plays an important role for appearance of cartilage tissue in ES cell transplanted joint

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

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