Recombinant Human Insulin-Like Growth Factor-I Stimulates in Vitro Matrix Synthesis and Cell Proliferation in Rabbit Flexor Tendon

Abstract

Summary:Flexor tendons have an intrinsic ability for repair, with a capacity to metabolize matrix components and to proliferate. To identify factors with the potential of affecting those abilities, the effects of recombinant human insulinlike growth factor (rhIGF-I), insulin and fetal calf serum (FCS) on the synthesis of proteoglycan, collagen, and non-collagen protein and cell proliferation were investigated in short-term explant cultures of the deep flexor tendon of the rabbit. Matrix synthesis and cell proliferation were stimulated dose dependently by rhIGF-I at doses between 10 and 250 and at 10-100 ng/ml, respectively, by insulin at 250-5,000 ng/ml, and by FCS at 2-15%. Estimated maximal stimulation (Emax) of up to three times the control value was observed with rhIGF-I at 250 ng/ml. Maximal stimulation was observed at 5,000 n g h l with insulin, and FCS at 15%. rhIGF-I was more potent than insulin in stimulating protein synthesis and cell proliferation. The Emax of stimulation of proteoglycan and collagen synthesis by rhIGF-I were two times that of FCS, and the Em,, of cell proliferation by FCS was twice that of rhIGF-I. Growth factors thus have the ability to stimulate matrix synthesis and cell proliferation in rabbit flexor tendon. This provides a rationale for further studies on the role of growth factors in flexor tendon healing in humans.

Effect of estrogen on tendon collagen synthesis, tendon structural characteristics, and biomechanical properties in postmenopausal women

“…Fluid collected from the interstitial fluid surrounding the patellar tendon by using a microdialysis technique was analyzed for a marker of CTX-I synthesis, the amino terminal propeptide of CTX-I (PINP) (31). The remaining dialysate was used for analyses of IGF-I and IGF-binding proteins (IGFBPs) (1)(2)(3)(4). After previous preparation of incision sites with local anesthetic (lidocaine 1%), ethylene oxide sterilized catheters with high molecular mass cut-off (3,000 kDa, membrane length 30 mm, inner diameter 0.50 mm) were inserted under ultrasound guidance in the peritendinous spaces of patellar tendons, as previously described (31).…”

“…These findings suggest a differential effect of estrogen in bone and tendons and estrogen in combination with mechanical loading. The effect may either be direct or an indirect effect of estrogen on other growth factors and cytokines known to influence collagen turnover, such as insulin-like growth factor-I (IGF-I) (2,6,8,43,56).…”

Structure of retracted tendons after staged repair following continuous traction

“…A large body of literature [7] focuses on factors that can lead to tendon rupture [2,23,28,29], on the immediate changes of the tendon architecture with disuse after rupture [19,21], and on the repair and healing of the tendon [1,4,6,12,24]. Furthermore, various reports document the effect of continuous lengthening of the normal tendon [9,10,34].…”

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.…”