Differential effects of insulin‐like growth factor‐I on matrix and DNA synthesis in various regions and types of rabbit tendons

Abstract

Tendon healing and integration of tendon grafts may be site or donor specific. To determine if differences exist in sensitivity to growth factors that have the potential to influence tendon repair, we compared the effects of recombinant human insulin-like growth factor-I on various types of tendon segments. The dose response effects on proteoglycan, collagen, noncollagen protein, and DNA synthesis were investigated in short-term explant cultures of intrasynovial intermediate and proximal segments of deep flexor tendons extrasynovial segments of deep flexor tendons, and Achilles tendons of rabbits. The four different types of tendon segments cultured in media without recombinant human insulin-like growth factor-I synthesized similar amounts of each of the matrix components. Intrasynovial proximal segments synthesized 15 times less DNA than other tendon segments. Recombinant human insulin-like growth factor-I stimulated matrix and DNA synthesis of all tendon segments in a dose-dependent manner in intervals from 10 to 1,000 ng/ml. The potency (LogED50) of the stimulation did not differ between the segments. The estimated maximal stimulation (E(max)) of proteoglycan synthesis by recombinant human insulin-like growth factor-I was higher, and of collagen and noncollagen protein synthesis was lower, in intrasynovial proximal segments as compared with that of the other types of segments. In contrast, the estimated maximal stimulation of DNA synthesis by recombinant human insulin-like growth factor-I was 6-fold higher than controls in all types of tendons. These findings demonstrate differences in mitotic capacity between anatomical regions of tendons during culture without recombinant human insulin-like growth factor-I and in matrix synthesis after stimulation with it.

Dose-related cellular effects of platelet-derived growth factor-BB differ in various types of rabbit tendons in vitro

“…The highest potency of synthesis of collagen and noncollagen protein and lowest potency of cell proliferation were seen in the proximal intrasynovial tendon segments. These results correlate with previous ndings that brocartilaginous-like regions in proximal intrasynovial exor tendons and extrasynovial tendons have different morpho- logical and biochemical characteristics and suggest that the sensitivity to PDGF-BB differs in various regions and types of tendon segments (Okuda et al 1987, Abrahamsson 1991, Abrahamsson and Lohmander 1996.…”

“…IGF-I dose-dependently stimulates cell proliferation and matrix synthesis with equal potencies, but with varying maximal responses in different tendon segments of rabbits (Abrahamsson and Lohmander 1996). In this study, PDGF-BB dose-dependently stimulated cell proliferation and matrix synthesis with equal maximal responses, but varying potencies.…”

“…Since IGF-I may be present in tendons and its stimulatory effects on cell proliferation and matrix synthesis differ in various types of tendons, one might speculate that the effects of PDGF-BB may vary in different types of tendons as well , Abrahamsson and Lohmander 1996, Murphy and Nixon 1997.…”

Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons

“…11 Previous work has demonstrated the value of growth factor injections, particularly insulinlike growth factor-I (IGF-I), to stimulate cellular proliferation and matrix synthesis in animal tendon and ligament models. [12][13][14][15][16][17][18][19][20] Although exogenous IGF-I has been shown to stimulate tendon healing in vivo in an equine model, 20 it has a short half-life, which necessitates repeated dosing, making clinical application challenging and costly. These problems could be abolished by a gene therapy approach to insert the IGF-I gene directly into healing tendon lesions.…”

Expression of insulin‐like growth factor binding proteins in healing tendon lesions

“…Exogenous IGF-I therapy improves tendon healing through the stimulation of extracellular matrix synthesis and cell proliferation. [1][2][3][4][5][6] These biological effects of IGF-I are exerted through the IGF system, a complex network of ligands, cell membrane receptors, and extracellular binding proteins that interact to regulate the activity of IGF-I. When IGF-I binds to the type I IGF receptor (IGF-IR) located in the target cell membrane, a complex signal transduction pathway is initiated, resulting in the modulation of gene expression and the upregulation of anabolic responses within the cell.…”