Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate

Rogachefsky, Richard A.; Dean, David D.; Howell, David S.; Altman, Roy D.

doi:10.1016/s1063-4584(05)80025-1

Cited by 112 publications

(85 citation statements)

References 33 publications

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“…In other research related to gene-modified bovine meniscal cells, adenovirusmediated hepatocyte growth factor gene therapy enhanced blood vessel formation in the subcutaneous pouch of athymic nude mice for 8 weeks [9]. The current research selected the hIGF-1 as the target cytokine because it plays a key role in the regulation of chondrocyte proteoglycan metabolism [21,25]: it is an important anabolic modulator of cartilage metabolism whose action is mediated by high-affinity cell surface receptors. It also plays an important role in stimulating collagen and proteoglycan synthesis in cartilage through an autocrine feedback mechanism [25].…”

Section: Discussionmentioning

confidence: 99%

“…The current research selected the hIGF-1 as the target cytokine because it plays a key role in the regulation of chondrocyte proteoglycan metabolism [21,25]: it is an important anabolic modulator of cartilage metabolism whose action is mediated by high-affinity cell surface receptors. 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].…”

Section: Discussionmentioning

confidence: 99%

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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%

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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“…IGF-I also exhibits anticatabolic effects on cartilage, inhibiting or counteracting endogenous [ 131 and exogenous [ 1 I] catabolic agents. In vivo, IGF-I is present in biologically active concentrations in both synovial fluid [28] and articular cartilage [lo], and has been reported to help induce articular cartilage repair [23]. To exert its biological effects, IGF-I must penetrate the cartilage matrix and bind to specific surface receptors [33] on the articular chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

The effect of dynamic compression on the response of articular cartilage to insulin‐like growth factor‐I

Bonassar

Grodzinsky

Frank

et al. 2001

Journal Orthopaedic Research

211

153

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Articular cartilage is routinely subjected to mechanical forces and to cell-regulatory molecules. Previous studies have shown that mechanical stimuli can influence articular chondrocyte metabolic activity, and biochemical studies have shown that growth factors and cytokines control many of the same cell functions. Little is known, however, of the relationships or interplay, if any, between these two key components of the articular environment. This study investigated the comparative and interactive effects of low amplitude, sinusoidal, dynamic compression and insulin-like growth factor-I (IGF-I), a polypeptide in synovial fluid that is anabolic for cartilage. In bovine patellofemoral cartilage explants, IGF-I increased protein and proteoglycan synthesis 90% and 120%, respectively while dynamic compression increased protein and proteoglycan synthesis 40Y1 and go%, respectively. Stimulation by IGF-I was significantly greater than by dynamic compression for both protein and proteoglycan synthesis. When applied together, the two stimuli enhanced protein and proteoglycan synthesis by 180% and 290%, respectively, a degree greater than that achieved by either stimulus alone. IGF-I augmented protein synthesis with a time constant of 12.2 h. Dynamic compression increased protein synthesis with a time constant of 2.9 h, a rate significantly faster than that of IGF-I, suggesting that these signals act via distinct cell activation pathways. When used together, dynamic compression and IGF-I acted with a time constant of 5.6 h. Thus, dynamic compression accelerated the biosynthetic response to IGF-I and increased transport of IGF-I into the articular cartilage matrix, suggesting that, in addition to independently stimulating articular chondrocytes, cyclic compression may improve the access of soluble growth factors to these relatively isolated cells.

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“…And if, as recently suggested, proteoglycans have the ability to bind I G F binding protein (IGFBP) (lo), this reduced proteoglycan breakdown may, in turn, have increased the binding of IGFBP. There may be other explanations for this observation (7), and investigations of the mechanisms of action would b e of great interest.…”

mentioning

confidence: 99%

“…This was shown both in vitro, where IGF-1 was found to reduce interleukin-1 (IL-1)-stimulated cartilage degradation (6), and in vivo in an experimental model of OA, in which therapeutically administered IGF-1 in combination with a synthetic protease inhibitor (sodium pentosan polysulfate [PPS]) produced significant improvement in several OA parameters compared with PPS alone (7). IGF-1 alone had no effect, and the IGF-1-treated cartilage was macroscopically similar to the untreated OA cartilage (7), which is consistent with previous data showing that arthritic chondrocytes are hyporesponsive to IGF-1 stimulation (8,9). The exact reason for the improvement when PPS and IGF-1 were administered together is presently unknown.…”

mentioning

confidence: 99%

Normal expression of type 1 insulin‐like growth factor receptor by human osteoarthritic chondrocytes with increased expression and synthesis of insulin‐like growth factor binding proteins

Tardif

Reboul

Pelletier

et al. 1996

Arthritis & Rheumatism

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Objective. Our previous research demonstrated that, in contrast to normal chondrocytes, human osteoarthritic (OA) chondrocytes were hyporesponsive to stimulation by insulin-like growth factor 1 (IGF-1). The aim of the present investigation was to examine whether this finding was due to an alteration in the level of IGF receptors (IGFRs) and/or IGF binding proteins (IGFBP).Methods. A quantitative reverse transcriptase polymerase chain reaction technique (RT-PCR) was used to measure the type 1 IGFR messenger RNA (mRNA) level, and Northern blotting was used to measure type 2 IGFR and IGFBP mRNA levels. Western immunoblotting was used to identify and measure IGFBP levels.Results. There were similar levels of type 1 IGFR mRNA in normal and OA chondrocytes. The level of type 2 IGFR mRNA, in which an increased amount of which can interfere with the biologic effects of IGF-1, was lower in OA chondrocytes compared with normal chondrocytes. Articular chondrocytes produced IGFBP-2, IGFBP-3, and IGFBP-4, and OA chondrocytes secreted and expressed higher amounts than did normal chondrocytes. There was also an increased level of IGFBP-3Supported by grants from The Arthritis Society. Ginette Tardif, PhD, Pascal Reboul, PhD, Jean-Pierre Pelletier, MD, Changshan Geng, PhD, Jean-Marie Cloutier, MD, Johanne Martel-Pelletier, PhD: University of Montreal, and Louis-Charles Simard Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada.Drs. Tardif and Reboul had an equal scientific input in the realization of this study.Address reprint requests to Johanne Martel-Pelletier, PhD, Rheumatic Disease Unit, Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec, H2L 4K8, Canada.Submitted for publication September 13, 1995; accepted in revised form January 17, 1996. in the OA chondrocyte lysates. IGFBPs 1,5, and 6 were not detectable.Conclusion. OA chondrocytes synthesize and express a larger amount of 3 IGFBPs. This observation, along with a lack of detectable change in type 1 IGFR mRNA level, suggests that the hyporesponsiveness of OA chondrocytes to IGF-1 might implicate the involvement of IGFBPs in this pathologic process.Osteoarthritis (OA) is characterized by a progressive degeneration and erosion of the cartilage, and it results from a failure of the chondrocyte to maintain the balance between synthesis and degradation of the extracellular matrix. The pathologic changes are related, depending on the stage of the disease, to a combination of both a degradation of the main components of the matrix and/or a decrease in the synthesis and/or quality of the matrix macromolecules (1). Among the constituents that play a role in the mechanism of cartilage repair are growth factors, such as insulin-like growth factor 1 (IGF-1) (2,3). This growth factor enhances the synthesis of collagen and proteoglycan (2-5). There is also evidence that it could play a role in the pathogenesis of OA. This was shown both in vitro, where IGF-1 was found to reduce interleukin-1 (IL-1)-stimulated cartilage degradation (6), and in vivo in an ...

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Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate

Cited by 112 publications

References 33 publications

Treating Human Meniscal Fibrochondrocytes with hIGF-1 Gene by Liposome

Treating Human Meniscal Fibrochondrocytes with hIGF-1 Gene by Liposome

The effect of dynamic compression on the response of articular cartilage to insulin‐like growth factor‐I

Normal expression of type 1 insulin‐like growth factor receptor by human osteoarthritic chondrocytes with increased expression and synthesis of insulin‐like growth factor binding proteins

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