The role of insulin-like growth factor-I in hyaluronan mediated repair of cultured cartilage explants

Homandberg, Gene A.; Ummadi, V.; Kang, Hellan

doi:10.1007/s00011-004-1276-y

Cited by 13 publications

(12 citation statements)

References 52 publications

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“…A similar result was seen in cartilage explants, when exposure of free HA led to retention of IGF-1. 41 We speculate that, without HA in the alginate matrix, exogenous IGF-1 delivery suppresses IGF-1 expression, although as HA is introduced into the matrix, HA begins to sequester exogenous IGF-1, promoting endogenous IGF-1 expression. Finally, as higher amounts of HA are included within the alginate matrix, higher amounts of IGF-1 are retained, thus increasing chondrocyte exposure to IGF-1 and decreasing IGF-1 endogenous expression.…”

Section: Discussionmentioning

confidence: 98%

Addition of Hyaluronic Acid to Alginate Embedded Chondrocytes Interferes with Insulin-like Growth Factor-1 SignalingIn VitroandIn Vivo

Yoon

Curtiss²,

Reddi³

et al. 2009

Tissue Engineering Part A

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The development of an engineered tissue requires a clear understanding of the interactions between the individual components. In this study, we investigated how the addition of hyaluronic acid (HA) to a cartilage tissue engineered scaffold alters chondrocytic expression, and specifically the expression of insulin-like growth factor-1 (IGF-1) signaling molecules. Bovine chondrocytes were embedded (7 million cells/mL) in 2.0% w/v alginate hydrogels containing varying HA concentrations (0, 0.05, 0.50, and 5.00 mg/mL). In vitro constructs were cultured with exogenous IGF-1, and gene expression was monitored at days 1, 4, and 8 for IGF-1, IGF-1 receptor (IGF-1R), IGF binding protein 3 (IGFBP-3), type II collagen and type I collagen. In vivo constructs were precultured for 24 h with exogenous IGF-1 before being implanted subcutaneously in severe combined immunodeficient mice; samples were analyzed using histology at days 7, 14, and 21. Results indicate that, with the addition of high levels (5.00 mg/mL) of HA, IGF-1 can become entrapped within the matrix and therefore interfere with the delivery of IGF-1 to chondrocytes. In vitro and in vivo data showed that increasing the concentration of HA in an alginate hydrogel can decrease chondrocyte IGF-1 expression. IGF-1R expression did not change with HA concentration, and the addition of any HA did not significantly alter IGFBP-3 expression. Chondrocytes continuously expressed phenotypic type II collagen in vitro and in vivo throughout the study for all the groups. However, for all the HA concentrations investigated, chondrocytes showed more of a fibroblastic phenotype, as indicated by greater expression of type I collagen than with no HA, in vitro and in vivo. In conclusion, these results indicate that HA interferes with the delivery of IGF-1 to chondrocytes, affecting the endogenous expression of IGF-1 signaling molecules and the resulting chondrocyte phenotype, and therefore demonstrating the critical effect of biomaterial scaffolds on encapsulated cell function.

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Section: Discussionmentioning

confidence: 98%

Addition of Hyaluronic Acid to Alginate Embedded Chondrocytes Interferes with Insulin-like Growth Factor-1 SignalingIn VitroandIn Vivo

Yoon

Curtiss²,

Reddi³

et al. 2009

Tissue Engineering Part A

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“…Similar opposing effects of Hyalovet and HYAL-2 were observed in in vitro-produced sheep embryos (Marei et al 2016a). Small-sized HA has been shown to regulate the expression of IGFs (Homandberg et al 2004) and heat shock proteins (Xu et al 2002), which are important for early embryo development in the oviduct (Aviles et al 2010). We concluded that the presence of large-size HA in the vicinity of developing embryos disturbs the oviductal environment and embryo development.…”

Section: Pre-implantation Embryo Developmentmentioning

confidence: 84%

Regulation and roles of the hyaluronan system in mammalian reproduction

et al. 2017

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Hyaluronan (HA) is a non-sulphated glycosaminoglycan polymer naturally occurring in many tissues and fluids of mammals, including the reproductive system. Its biosynthesis by HA synthase (HAS1-3) and catabolism by hyaluronidases (HYALs) are affected by ovarian steroid hormones. Depending upon its molecular size, HA functions both as a structural component of tissues in the form of high-molecular-weight HA or as a signalling molecule in the form of small HA molecules or HA fragments with effects mediated through interaction with its specific cell-membrane receptors. HA is produced by oocytes and embryos and in various segments of the reproductive system. This review provides information about the expression and function of members of the HA system, including HAS, HYALs and HA receptors. We examine their role in various processes from folliculogenesis through oocyte maturation, fertilisation and early embryo development, to pregnancy and cervical dilation, as well as its application in assisted reproduction technologies. Particular emphasis has been placed upon the role of the HA system in pre-implantation embryo development and embryo implantation, for which we propose a hypothetical sequential model. Reproduction (2017) 153 R43-R58

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“…It was found that HA decreased release of IGF-I into the media and enhanced retention of fluorescently labeled IGF-I added to cartilage explants [56]. In order to implicate IGF-I further, the IGF-I blocker, rhIGF-I binding protein-2 was tested, which blocks access of IGF-I to its receptor, and found that it decreased the ability of HA to enhance PG synthesis and blocked the ability of HA to facilitate restoration of PG in Fn-f damaged cartilage [56]. Thus, HA compensated for Fn-f mediated damage through its ability to enhance PG synthesis through elevated activity of IGF-I.…”

Section: Introductionmentioning

confidence: 98%

“…IGF-I is the major PG synthesis promoting factor in cartilage and is known to be stored in the matrix [55]. It was found that HA decreased release of IGF-I into the media and enhanced retention of fluorescently labeled IGF-I added to cartilage explants [56]. In order to implicate IGF-I further, the IGF-I blocker, rhIGF-I binding protein-2 was tested, which blocks access of IGF-I to its receptor, and found that it decreased the ability of HA to enhance PG synthesis and blocked the ability of HA to facilitate restoration of PG in Fn-f damaged cartilage [56].…”

Section: Introductionmentioning

confidence: 98%

Mechanisms of Beneficial Effects of High Molecular Weight Hyaluronan on Cultured Cartilage Tissue

Homandberg¹

2006

CRR

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The efficacy of high molecular weight hyaluronan (HA) in reversing cartilage damage in patients with joint degeneration has not yet been clearly demonstrated, although there is compelling evidence of reduction in parameters of pain. The rationales as to why HA may be beneficial to cartilage structure are diverse and are largely based on studies of in vitro models of cartilage damage. However, there are few studies in these models showing a linkage between effects of HA on cartilage metabolism to an outcome more closely related to osteoarthritis, such as cartilage matrix degradation. Thus, while HA may have a myriad of effects on chondrocytes, perhaps not all of these explain its potential chondroprotective activity. This review discusses selected studies and question whether there is a common explanation for efficacy of HA. It is concluded and proposed that HA may be a weak catabolic mediator that stimulates anabolic processes in cartilage. Thus, the efficacy of HA may be explained by the linkage of catabolic events to subsequent anabolic reparative responses, a newer theme supported by numerous studies.

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The role of insulin-like growth factor-I in hyaluronan mediated repair of cultured cartilage explants

Abstract: The reparative effects of HA appear to involve enhanced PG synthesis through IGF-1 and requires cartilage matrix.

Cited by 13 publications

References 52 publications

Addition of Hyaluronic Acid to Alginate Embedded Chondrocytes Interferes with Insulin-like Growth Factor-1 SignalingIn VitroandIn Vivo

Addition of Hyaluronic Acid to Alginate Embedded Chondrocytes Interferes with Insulin-like Growth Factor-1 SignalingIn VitroandIn Vivo

Regulation and roles of the hyaluronan system in mammalian reproduction

Mechanisms of Beneficial Effects of High Molecular Weight Hyaluronan on Cultured Cartilage Tissue

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