Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

Nielsen, Rikke Vibeke; Holm, Lars; Malmgaard-Clausen, Nikolaj Mølkjær; Reitelseder, Søren; Heinemeier, Katja Maria; Kjær, Michael

doi:10.1152/japplphysiol.01084.2013

Cited by 30 publications

(35 citation statements)

References 23 publications

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“…To further explore the difference in size between tendons of Scx:IGF1R + and Scx:IGF1R Δ mice, we determined whether IGF1 regulated general protein synthesis. IGF1 is known to activate the PI3K/Akt pathway, which increases protein synthesis in skeletal muscle (1), and local IGF1 can increase the protein fractional synthesis rate in tendons of elderly men and patients with Ehlers‐Danlos syndrome (13, 44). Using the SUnSET technique (20, 21), we observed that treating tenocytes with IGF1 doubled protein synthesis rates, and blocking Akt phosphorylation returned protein synthesis levels to baseline.…”

Section: Discussionmentioning

confidence: 99%

Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth

et al. 2019

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Tenocytes serve to synthesize and maintain collagen fibrils and other extracellular matrix proteins in tendon. Despite the high prevalence of tendon injury, the underlying biologic mechanisms of postnatal tendon growth and repair are not well understood. IGF1 plays an important role in the growth and remodeling of numerous tissues but less is known about IGF1 in tendon. We hypothesized that IGF1 signaling is required for proper tendon growth in response to mechanical loading through regulation of collagen synthesis and cell proliferation. To test this hypothesis, we conditionally deleted the IGF1 receptor (IGF1R) in scleraxis (Scx)‐expressing tenocytes using a tamoxifen‐inducible Cre‐recombinase system and caused tendon growth in adult mice via mechanical overload of the plantaris tendon. Compared with control Scx‐expressing IGF1R‐positive (Scx:IGF1R+) mice, in which IGF1R is present in tenocytes, mice that lacked IGF1R in their tenocytes [Scx‐expressing IGF1R‐negative (Scx:IGF1RΔ) mice] demonstrated reduced cell proliferation and smaller tendons in response to mechanical loading. Additionally, we identified that both the PI3K/protein kinase B and ERK pathways are activated downstream of IGF1 and interact in a coordinated manner to regulate cell proliferation and protein synthesis. These studies indicate that IGF1 signaling is required for proper postnatal tendon growth and support the potential use of IGF1 in the treatment of tendon disorders.—Disser, N. P., Sugg, K. B., Talarek, J. R., Sarver, D. C., Rourke, B. J., Mendias, C. L. Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth. FASEB J. 33, 12680–12695 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth

et al. 2019

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“…Evidence from in vitro studies of chondrocytes (Martin et al., ; Loeser et al., ) and in vivo study of osteoblasts (Cao et al., ) suggests that cells in older individuals have a reduced capacity to respond to IGF‐1. Recent work however has shown that local injection of IGF‐1 into the patellar tendon of young and old men is able to stimulate protein synthesis to an equal degree demonstrating that the ability to respond to anabolic stimuli is maintained in older age (Nielsen et al., ).…”

Section: Discussionmentioning

confidence: 99%

Ageing does not result in a decline in cell synthetic activity in an injury prone tendon

Thorpe

McDermott

Goodship

et al. 2015

Scandinavian Med Sci Sports

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1Advancing age is a well-known risk factor for tendon disease. Energy storing tendons, (e.g. 2human Achilles, equine superficial digital flexor tendon (SDFT)) are particularly vulnerable 3 and it is thought that injury occurs following an accumulation of micro-damage in the 4 extracellular matrix (ECM). Several authors suggest that age-related micro-damage 5 accumulates due to a failure of the aging cell population to maintain the ECM or an 6 imbalance between anabolic and catabolic pathways. We hypothesised that ageing results in a 7 decreased ability of tendon cells to synthesise matrix components and matrix degrading 8 enzymes, resulting in a reduced turnover of the ECM and a decreased ability to repair micro-9 damage. The SDFT was collected from horses aged 3-30 years with no signs of tendon 10 injury. Cell synthetic and degradative ability was assessed at the mRNA and protein levels. 11Telomere length was measured as an additional marker of cell ageing. There was no decrease 12 in cellularity or relative telomere length with increasing age, and no decline in mRNA or 13 protein levels for matrix proteins or degradative enzymes. The results suggest that the 14 mechanism for age-related tendon deterioration is not due to reduced cellularity or a loss of 15 synthetic functionality and that alternative mechanisms should be considered.

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“…IGF‐1 has been shown to have versatile roles in tissue engineering including mitotic and anabolic effects . Protein insulin is structurally analogous to IGF‐1 and has been shown to bind to IGF‐1 receptors to elicit similar effects yet is more widely available at lower costs than IGF‐1.…”

Section: Resultsmentioning

confidence: 99%

“…Mitotic effects of IGF‐1 in tendon cells and tendon animal models have also been well documented . IGF‐1 has also been observed to increase collagen synthesis . For example, injection of IGF‐1 was shown to increase collagen content near the injection site .…”

Section: Introductionmentioning

confidence: 99%

Insulin immobilized PCL‐cellulose acetate micro‐nanostructured fibrous scaffolds for tendon tissue engineering

Ramos

Abdulmalik

Arul

et al. 2019

Polymers for Advanced Techs

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Use of growth factors as biochemical molecules to elicit cellular differentiation is a common strategy in tissue engineering. However, limitations associated with growth factors, such as short half‐life, high effective physiological doses, and high costs, have prompted the search for growth factor alternatives, such as growth factor mimics and other proteins. This work explores the use of insulin protein as a biochemical factor to aid in tendon healing and differentiation of cells on a biomimetic electrospun micro‐nanostructured scaffold. Dose response studies were conducted using human mesenchymal stem cells (MSCs) in basal media supplemented with varied insulin concentrations. A dose of 100‐ng/mL insulin showed increased expression of tendon markers. Synthetic‐natural blends of various ratios of polycaprolactone (PCL) and cellulose acetate (CA) were used to fabricate micro‐nanofibers to balance physicochemical properties of the scaffolds in terms of mechanical strength, hydrophilicity, and insulin delivery. A 75:25 ratio of PCL:CA was found to be optimal in promoting cellular attachment and insulin immobilization. Insulin immobilized fiber matrices also showed increased expression of tendon phenotypic markers by MSCs similar to findings with insulin supplemented media, indicating preservation of insulin bioactivity. Insulin functionalized scaffolds may have potential applications in tendon healing and regeneration.

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Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

Cited by 30 publications

References 23 publications

Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth

Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth

Ageing does not result in a decline in cell synthetic activity in an injury prone tendon

Insulin immobilized PCL‐cellulose acetate micro‐nanostructured fibrous scaffolds for tendon tissue engineering

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