Expression of insulin-like growth factor binding proteins in healing tendon lesions.
Abstract: he treatment of overuse tendon injuries with exogenous growth factors such as insulin-like growth factor-I (IGF-I) may facilitate an improved return to sustained athletic function. The biological effects of IGF-I are exerted under the control of a complex of IGF receptors, binding proteins, and proteases. This IGF system includes a family of six structurally related high-affinity IGF binding proteins (IGFBPs) that protect IGF-I from local proteases and restrict access of IGF-I to its receptor. This study describes the expression of the IGFBPs in flexor tendon after acute injury and during healing over time. Collagenase-induced lesions were created in the tensile region of the flexor digitorum superficialis tendon of both forelimbs of 14 horses. Tendons were harvested from euthanatized horses 1, 2, 4, 8, or 24 weeks following injury. Gene expression was quantitated by fluorescent real-time PCR, and protein expression was evaluated by Western ligand blot (WLB). Message for IGFBPs 2 to 6 was expressed in both normal and healing tendon. No IGFBP-1 mRNA was detected in equine tendon. Message expression for IGFBP-2, -3, and -4 increased following injury, whereas message expression for IGFBP-5 and -6 decreased. Protein expression for IGFBP-2, -3, and -4 was detected by WLB in normal tendon and showed a marked increase following injury. Protein for IGFBP-5 and -6 was not detectable by WLB in normal or healing tendon. The results of this study document the IGFBP response of flexor tendons to injury and healing, which provides information necessary for the design of protocols that may enhance tendon healing through manipulation of IGF-I ligand and binding protein levels.
(c) 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
Publication Date: 2006-01-26 PubMed ID: 16435347DOI: 10.1002/jor.20000Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
Summary
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This research investigates how insulin-like growth factor binding proteins (IGFBPs) respond during the healing process of horse tendon injuries, providing insights that may enhance healing interventions involving the manipulation of insulin-like growth factor-I (IGF-I) and binding proteins.
About the Insulin-like Growth Factor System
- The insulin-like growth factor (IGF) system is a biological process which involves a complex of IGF receptors, binding proteins and proteases.
- Prominently, this system includes the family of six structurally related high-affinity IGF binding proteins (IGFBPs). These proteins protect IGF-I from local proteases and restrict access of IGF-I to its receptor.
- Manipulating this IGF system, specifically through the application of growth factors like IGF-I, has potential to support improved healing in overuse tendon injuries, thereby facilitating the return to athletic function.
The Experiment and Its Findings
- The researchers created collagenase-induced lesions in the flexor tendons of 14 horses and closely observed the healing process over periods of 1, 2, 4, 8, or 24 weeks after the injury.
- To monitor the evolution of IGFBPs during the healing process, gene expression was quantified using fluorescent real-time PCR, and protein expression was evaluated with Western Ligand Blot (WLB).
- The study found that IGFBPs 2 to 6 were expressed in both normal and healing tendons. However, there was no detection of IGFBP-1 mRNA in the equine tendon.
- Expression for IGFBP-2, -3, and -4 increased after injury, and conversely, expression for IGFBP-5 and -6 decreased. However, protein for IGFBP-5 and -6 was not detectable by WLB in normal or healing tendon.
Implications of the Study
- The findings of the study document the IGFBP response of flexor tendons during injury and healing, outlining how IGFBPs are involved in the healing process of overuse tendon injuries in horses.
- This research progresses understanding of the IGF system’s function in healing processes, which adds value to the design of protocols aimed at enhancing tendon healing. Harnessing this information could lead to methods that involve manipulating IGF-I ligand and binding protein levels to facilitate and expedite healing.
Cite This Article
APA
Dahlgren LA, Mohammed HO, Nixon AJ.
(2006).
Expression of insulin-like growth factor binding proteins in healing tendon lesions.
J Orthop Res, 24(2), 183-192.
https://doi.org/10.1002/jor.20000 Publication
Researcher Affiliations
- Comparative Orthopaedics Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
MeSH Terms
- Animals
- Blotting, Western
- Disease Models, Animal
- Female
- Gene Expression
- Horses
- Insulin-Like Growth Factor Binding Proteins / genetics
- Insulin-Like Growth Factor Binding Proteins / metabolism
- Male
- RNA, Messenger / analysis
- Reverse Transcriptase Polymerase Chain Reaction
- Tendon Injuries / metabolism
- Tendon Injuries / pathology
- Tendons / metabolism
- Tendons / pathology
- Wound Healing / physiology
Grant Funding
- AR08587 / NIAMS NIH HHS
Citations
This article has been cited 5 times.- Roberts JH, Halper J. Growth Factor Roles in Soft Tissue Physiology and Pathophysiology.. Adv Exp Med Biol 2021;1348:139-159.
- Ragni E, Papait A, Perucca Orfei C, Silini AR, Colombini A, Viganò M, Libonati F, Parolini O, de Girolamo L. Amniotic membrane-mesenchymal stromal cells secreted factors and extracellular vesicle-miRNAs: Anti-inflammatory and regenerative features for musculoskeletal tissues.. Stem Cells Transl Med 2021 Jul;10(7):1044-1062.
- de Cesar Netto C, Godoy-Santos AL, Augusto Pontin P, Natalino RJM, Pereira CAM, Lima FDO, da Fonseca LF, Staggers JR, Cavinatto LM, Schon LC, de Camargo OP, Fernandes TD. Novel animal model for Achilles tendinopathy: Controlled experimental study of serial injections of collagenase in rabbits.. PLoS One 2018;13(2):e0192769.
- Chen J, Zhang E, Zhang W, Liu Z, Lu P, Zhu T, Yin Z, Backman LJ, Liu H, Chen X, Ouyang H. Fos Promotes Early Stage Teno-Lineage Differentiation of Tendon Stem/Progenitor Cells in Tendon.. Stem Cells Transl Med 2017 Nov;6(11):2009-2019.
- Watts AE, Yeager AE, Kopyov OV, Nixon AJ. Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.. Stem Cell Res Ther 2011 Jan 27;2(1):4.
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