Contribution of insulin-like growth factor-1 to tendon repair (Review)

Tendinopathy is a common musculoskeletal disorder that markedly diminishes both physical performance and overall quality of life across age groups, imposing considerable socio-economic burdens. Insulin-like growth factor-1 (IGF-1) functions as a protective cytokine with significant involvement in multiple pathological conditions, including tendinopathy. The present review integrated current evidence on the role of IGF-1 in tendon repair. IGF-1 actively participates in every phase of tendon repair, making it a central driver of the injury response. When administered for tendon repair, IGF-1 binds to IGF-1R on target cell membranes, initiating sequential phosphorylation cascades that transmit signals from the membrane to the nucleus, while IGFBPs finely modulate this process. These intricate signaling pathways ultimately yield beneficial effects such as reduced inflammation, enhanced cell proliferation and migration and increased collagen synthesis, thereby promoting restoration of tendon structure and integrity. IGF-1 has emerged as one of the most promising growth factors in tendon regenerative strategies. Nevertheless, clarification of critical parameters such as administration dosage and timing remains necessary to optimize its therapeutic value and to fully delineate its contribution to tendon repair.

• Publication year

  2025

• Venue

  International Journal of Molecular Medicine

• Publication date

  2025-09-11

• Fields of study

  Medicine

• Identifiers
  DOI 10.3892/ijmm.2025.5636PMID 40937584PMCID 12440272
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Echinacoside promotes collagen synthesis and survival via activation of IGF‐1 signaling to alleviate UVB‐induced dermal fibroblast photoaging

  2025cited by this paper
• Insulin-like growth factor-1 (IGF-1) empowering tendon regenerative therapies

  2025cited by this paper
• Challenges of insulin-like growth factor-1 testing

  2024cited by this paper
• Reprogramming tendon healing: a guide to novel molecular tools

  2024cited by this paper
• Therapeutic potential of GDF-5 for enhancing tendon regenerative healing

  2024cited by this paper
• IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-κB signaling pathways to promote wound healing.

  2024cited by this paper
• Current progress in growth factors and extracellular vesicles in tendon healing

  2023cited by this paper
• In Vitro and In Vivo Effects of IGF-1 Delivery Strategies on Tendon Healing: A Review

  2023influential reference
• Secretome from myoblasts statically loaded at low intensity promotes tenocyte proliferation via the IGF‐1 receptor pathway

  2023cited by this paper
• Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair

  2023influential reference
• The effects of NF‐κB suppression on the early healing response following intrasynovial tendon repair in a canine model

  2023cited by this paper
• Insulin-like growth factor binding protein 4 loaded electrospun membrane ameliorating tendon injury by promoting retention of IGF-1.

  2023cited by this paper
• Tendon-regulating and bone-setting manipulation promotes the recovery of synovial inflammation in rabbits with knee osteoarthritis via the TLR4–MyD88–NF-κB signaling pathway

  2023cited by this paper
• Insulin-Like Growth Factor-1 Promotes Human Uterine Leiomyoma Cell Proliferation via PI3K/AKT/mTOR Pathway

  2022cited by this paper
• Pegylated insulin-like growth factor-1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model.

  2022cited by this paper
• Challenges and perspectives of tendon-derived cell therapy for tendinopathy: from bench to bedside

  2022cited by this paper
• The History of the Insulin-Like Growth Factor System

  2022cited by this paper
• Biological response of extracorporeal shock wave therapy to tendinopathy in vivo (review)

  2022cited by this paper
• PI3K Isoform-Specific Regulation of Leader and Follower Cell Function for Collective Migration and Proliferation in Response to Injury

  2022cited by this paper
• A Promising Candidate in Tendon Healing Events—PDGF-BB

  2022cited by this paper
• Insulin-Like Growth Factor 1 Attenuates the Pro-Inflammatory Phenotype of Neutrophils in Myocardial Infarction

  2022cited by this paper
• Morphological changes of macrophages and their potential contribution to tendon healing.

  2021cited by this paper
• Tendinopathy

  2021cited by this paper
• mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events.

  2021cited by this paper
• The Effect of Insulin and Insulin-like Growth Factor 1 (IGF-1) on Cellular Proliferation and Migration of Human Subacromial Bursa Tissue

  2021cited by this paper
• Efficacy and Mechanism of Electroacupuncture Treatment of Rabbits With Different Degrees of Knee Osteoarthritis: A Study Based on Synovial Innate Immune Response

  2021cited by this paper
• Reparative and Maladaptive Inflammation in Tendon Healing

  2021cited by this paper
• No Treatment Benefits of Local Administration of Insulin-like Growth Factor-1 in Addition to Heavy Slow Resistance Training in Tendinopathic Human Patellar Tendons: A Randomized, Double-Blind, Placebo-Controlled Trial With 1-Year Follow-up

  2021influential reference
• The Role of the Non-Collagenous Extracellular Matrix in Tendon and Ligament Mechanical Behavior: A Review.

  2021cited by this paper
• Ginsenoside Rg1 enhances the healing of injured tendon in achilles tendinitis through the activation of IGF1R signaling mediated by oestrogen receptor

  2021cited by this paper
• High rates of calcium free diffusion in the cytosol of living cells.

  2021cited by this paper
• GH Deficiency and Replacement Therapy in Hypopituitarism: Insight Into the Relationships With Other Hypothalamic-Pituitary Axes

  2021cited by this paper
• GH and IGF-1 Replacement in Children.

  2020cited by this paper
• Tendon explant models for physiologically relevant in vitro study of tissue biology – a perspective

  2020cited by this paper
• TLR4 knockdown by miRNA-140-5p improves tendinopathy: an in vitro study

  2020cited by this paper
• Association of estrogen receptor β polymorphisms with posterior tibial tendon dysfunction

  2020cited by this paper
• Improving musculoskeletal health for children and young people – A ‘call to action’

  2020cited by this paper
• Local delivery of insulin/IGF-1 for bone regeneration: carriers, strategies, and effects

  2020cited by this paper
• Targeting the NF-κB signaling pathway in chronic tendon disease

  2019cited by this paper
• Ranking migration cue contributions to guiding individual fibroblasts faced with a directional decision in simple microfluidic bifurcations.

  2019cited by this paper
• Sorghumol triterpene inhibits the growth of circulating renal cancer cells by promoting cell apoptosis, G2/M cell cycle arrest and downregulating m-TOR/PI3K/AKT signalling pathway.

  2019cited by this paper
• Insulin-like growth factor binding protein (IGFBP6) is a cross-species tendon marker.

  2019cited by this paper
• Lanatoside C Induces G2/M Cell Cycle Arrest and Suppresses Cancer Cell Growth by Attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR Signaling Pathways

  2019cited by this paper
• Insulin‐like growth factor 1 signaling in tenocytes is required for adult tendon growth

  2019influential reference
• Intratendon delivery of leukocyte‐rich platelet‐rich plasma at early stage promotes tendon repair in a rabbit Achilles tendinopathy model

  2019cited by this paper
• Current trends in tendinopathy management.

  2019influential reference
• The Role of Insulin/IGF-1/PI3K/Akt/GSK3β Signaling in Parkinson's Disease Dementia

  2018cited by this paper
• The big five in fibrosis: Macrophages, myofibroblasts, matrix, mechanics, and miscommunication.

  2018cited by this paper
• IGF1 receptor signaling pathways.

  2018influential reference
• Role of IGF-binding proteins in regulating IGF responses to changes in metabolism.

  2018cited by this paper
• Activation of AKT‐mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells

  2018cited by this paper
• IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?

  2018cited by this paper
• Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be.

  2017cited by this paper
• The effect of estrogen on tendon and ligament metabolism and function.

  2017cited by this paper
• mTOR Signaling in Growth, Metabolism, and Disease.

  2017cited by this paper
• New insights into the role of mitochondrial calcium homeostasis in cell migration

  2017cited by this paper
• Anti-inflammatory effect of Cortex Eucommiae via modulation of the toll-like receptor 4 pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages.

  2017cited by this paper
• IGF-binding proteins.

  2017cited by this paper
• Musculoskeletal Disorders: A Neglected Group at Public Health and Epidemiology Meetings?

  2017cited by this paper
• The role of the IGF-1 Ec in myoskeletal system and osteosarcoma pathophysiology.

  2016cited by this paper
• Growth Hormone and Insulin-Like Growth Factor-1.

  2016cited by this paper
• In vitro two‐dimensional and three‐dimensional tenocyte culture for tendon tissue engineering

  2016influential reference
• Spontaneous rupture of the long head of the biceps tendon in a woman with hypothyroidism: a case report

  2016cited by this paper
• Tendinopathy

  2016cited by this paper
• Endothelial IGF-1 Receptor Signalling in Diabetes and Insulin Resistance.

  2016cited by this paper
• Sex Hormones and Tendon.

  2016cited by this paper
• Reference Values for IGF-I Serum Concentrations: Comparison of Six Immunoassays

  2016cited by this paper
• Gene regulation in the immediate-early response process.

  2016cited by this paper
• Monocyte/Macrophage-derived IGF-1 Orchestrates Murine Skeletal Muscle Regeneration and Modulates Autocrine Polarization.

  2015cited by this paper
• Use of ultrasound-targeted microbubble destruction to transfect IGF-1 cDNA to enhance the regeneration of rat wounded Achilles tendon in vivo

  2015influential reference
• Calcium signaling and cell proliferation.

  2015cited by this paper
• Insulin-like growth factor binding-protein-3 (IGFBP-3).

  2015cited by this paper
• Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue.

  2015cited by this paper
• Resolving an inflammatory concept: The importance of inflammation and resolution in tendinopathy

  2014cited by this paper
• Function of matrix IGF-1 in coupling bone resorption and formation

  2014cited by this paper
• Are Orai1 and Orai3 channels more important than calcium influx for cell proliferation?

  2014cited by this paper
• Resveratrol inhibits collagen I synthesis by suppressing IGF-1R activation in intestinal fibroblasts.

  2014cited by this paper
• Involvement of IGF-I receptor and estrogen receptor pathways in the protective effects of ginsenoside Rg1 against Aβ₂₅₋₃₅-induced toxicity in PC12 cells.

  2013cited by this paper
• Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions

  2013influential reference
• Atrogin-1, MuRF-1, and sarcopenia

  2013cited by this paper
• Morphine Prevents Lipopolysaccharide-Induced TNF Secretion in Mast Cells Blocking IκB Kinase Activation and SNAP-23 Phosphorylation: Correlation with the Formation of a β-Arrestin/TRAF6 Complex

  2013cited by this paper
• Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

  2013cited by this paper
• PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1

  2013cited by this paper
• Insulin-like growth factors in the gastrointestinal tract and liver.

  2012cited by this paper
• Optimization of Human Tendon Tissue Engineering: Synergistic Effects of Growth Factors for Use in Tendon Scaffold Repopulation

  2012cited by this paper
• mTOR signaling in growth control and disease.

  2012cited by this paper
• NF-κB, the first quarter-century: remarkable progress and outstanding questions.

  2012cited by this paper
• Effects of Differences in Lipid A Structure on TLR4 Pro-Inflammatory Signaling and Inflammasome Activation

  2012cited by this paper
• Insulin-like growth factor-1 promotes wound healing in estrogen-deprived mice: new insights into cutaneous IGF-1R/ERα cross talk.

  2012cited by this paper
• The effect of growth factors on both collagen synthesis and tensile strength of engineered human ligaments.

  2012cited by this paper
• Suppression of Nuclear Factor-κB Activation and Inflammation in Microglia by Physically Modified Saline*

  2012cited by this paper
• Development of a Refined Tenocyte Differentiation Culture Technique for Tendon Tissue Engineering

  2012cited by this paper
• Comparison of equine tendon- and bone marrow-derived cells cultured on tendon matrix with or without insulin-like growth factor-I supplementation.

  2012cited by this paper
• Local administration of insulin‐like growth factor‐I (IGF‐I) stimulates tendon collagen synthesis in humans

  2012cited by this paper
• Insulin-Like Growth Factor (IGF) Binding Protein 2 Functions Coordinately with Receptor Protein Tyrosine Phosphatase β and the IGF-I Receptor To Regulate IGF-I-Stimulated Signaling

  2012cited by this paper
• The effect of anisotropic collagen-GAG scaffolds and growth factor supplementation on tendon cell recruitment, alignment, and metabolic activity.

  2011cited by this paper
• mTOR signaling in disease.

  2011cited by this paper
• Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models

  2011cited by this paper
• IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling

  2011cited by this paper
• Bone marrow-derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin.

  2011cited by this paper

• Beyond VEGF and TGF-β: A Comprehensive Review of Growth Factor Pathways in the Pathophysiology of Uterine Leiomyomas

  2026cites this paper
• Beyond Platelet Count: Rethinking Platelet-Rich Plasma Efficacy Through Growth Factor Biology and Functional Quality.

  2026cites this paper
• IGFBP-6 as a potential therapeutic target in musculoskeletal disorders.

  2026cites this paper
• Challenge of Corneal Ulcer Healing: A Novel Conceptual Framework, the “Triad” of Corneal Ulcer Healing/Corneal Neovascularization/Intraocular Pressure, and Avascular Tendon Healing, for Evaluation of Corneal Ulcer Therapy, Therapy of Neovascularization, Glaucoma Therapy, and Pentadecapeptide BPC 157

  2025cites this paper