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European cells & materials2019; 38; 123-136; doi: 10.22203/eCM.v038a10

Insulin-like growth factor binding protein (IGFBP6) is a cross-species tendon marker.

Abstract: The main challenge in tendon injury management is suboptimal tissue healing that fails to re-establish original tendon function. Tissue bioengineering is a promising approach for tendon therapy, with potential to improve its functional outcomes. However, evaluation criteria for tissue-engineered tendon are unclear due to the lack of specific markers of differentiated tendon. The study aim was to identify a panel of genes that characterised tendons in comparison to cartilage or muscles and validate those genes, both in human and key species used as models for tendon diseases. Gene expression profiling of rat tendon and cartilage in whole-tissue samples and primary tenocytes and chondrocytes was undertaken using two independent microarray platforms. Genes that demonstrated high expression correlation across two assays were validated by qRT-PCR in rat tendon relative to cartilage and muscle. Five genes demonstrating the highest tendon-related expression in the validation experiment (ASPN, ECM1, IGFBP6, TNMD, THBS4) were further evaluated by qRT-PCR in ovine, equine and human tissue. The group of tendon markers, identified by unbiased transcriptomic analysis of rat musculoskeletal tissues, demonstrated species-dependent profiles of expression. Insulin-like growth factor binding protein 6 (IGFBP6) was identified as the only universal tendon marker. Further investigation in equine tendon showed that IGFBP6 expression was not affected by ageing or tendon function but decreased in anatomical regions subjected to elevated compressive force. IGFBP6 is a robust cross-species marker of tendon phenotype and may find application in evaluation of tendon physiology and guided differentiation of permissive cells towards functional tenocytes.
Publication Date: 2019-09-24 PubMed ID: 31550047DOI: 10.22203/eCM.v038a10Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research identifies Insulin-like growth factor binding protein 6 (IGFBP6) as a universal marker across different species for tendon identification, which could be beneficial for cellular differentiation in tissue bioengineering for tendon repair.

Background

  • The need for this research arises from the challenges in managing tendon injuries which often result in imperfect healing, leaving the tendon with suboptimal functionality.
  • For bioengineering tissues that can enhance tendon healing and improve function, there is a previously unidentified requirement for specific markers that indicate different stages of tendon differentiation.

Methodology

  • The researchers have used gene expression profiling of rat tendon and cartilage in both whole-tissue samples and primary tenocytes and chondrocytes, using two independent microarray platforms.
  • Genes that exhibited high expression correlation across the two assays were further validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) relative to cartilage and muscle in the rat.

Results

  • Five genes (ASPN, ECM1, IGFBP6, TNMD, THBS4) with the highest tendon-related expression in the validation experiment were further evaluated by qRT-PCR in ovine, equine, and human tissue.
  • These identified tendon markers showed variable expression profiles across different species.
  • However, the study identified Insulin-like growth factor binding protein 6 (IGFBP6) as a consistent tendon marker across all species.
  • Further analysis in equines revealed that IGFBP6 expression remained unaffected by age or tendon function but diminished in areas subjected to higher compressive forces.

Conclusions

  • IGFBP6 potentially serves as a robust cross-species identifier of tendons, beneficial in assessing tendon physiology and guided differentiation of cells towards functional tenocytes during tissue bioengineering applications.

Cite This Article

APA
Turlo AJ, Mueller-Breckenridge AJ, Zamboulis DE, Tew SR, Canty-Laird EG, Clegg PD. (2019). Insulin-like growth factor binding protein (IGFBP6) is a cross-species tendon marker. Eur Cell Mater, 38, 123-136. https://doi.org/10.22203/eCM.v038a10

Publication

ISSN: 1473-2262
NlmUniqueID: 100973416
Country: Switzerland
Language: English
Volume: 38
Pages: 123-136

Researcher Affiliations

Turlo, A J
  • Institute of Ageing and Chronic Disease, William Henry Duncan Building, 6 West Derby Street, L7 8TX Liverpool, UK.a.turlo@liverpool.ac.uk.
Mueller-Breckenridge, A J
    Zamboulis, D E
      Tew, S R
        Canty-Laird, E G
          Clegg, P D

            MeSH Terms

            • Animals
            • Biomarkers / metabolism
            • Cells, Cultured
            • Extracellular Matrix Proteins / genetics
            • Extracellular Matrix Proteins / metabolism
            • Horses
            • Humans
            • Insulin-Like Growth Factor Binding Protein 6 / genetics
            • Insulin-Like Growth Factor Binding Protein 6 / metabolism
            • Rats
            • Sheep
            • Species Specificity
            • Tendons / metabolism
            • Tenocytes / metabolism
            • Tissue Engineering / methods
            • Transcriptome

            Grant Funding

            • MR/P020941/1 / Medical Research Council

            Citations

            This article has been cited 6 times.
            1. Ramos-Mucci L, Sarmiento P, Little D, Snelling S. Research perspectives-Pipelines to human tendon transcriptomics. J Orthop Res 2022 May;40(5):993-1005.
              doi: 10.1002/jor.25315pubmed: 35239195google scholar: lookup
            2. Leek CC, Soulas JM, Sullivan AL, Killian ML. Using tools in mechanobiology to repair tendons. Curr Tissue Microenviron Rep 2020 Jun;1(2):31-40.
              doi: 10.1007/s43152-020-00005-wpubmed: 33585822google scholar: lookup
            3. Chen Y, Zhu Y, Song S, Hu Y. Contribution of insulin‑like growth factor‑1 to tendon repair (Review). Int J Mol Med 2025 Nov;56(5).
              doi: 10.3892/ijmm.2025.5636pubmed: 40937584google scholar: lookup
            4. Dossybayev K, Amandykova M, Orakbayeva A, Adylkanova S, Kozhakhmet A, Yergali K, Kulboldin T, Kulataev B, Torekhanov A. Genome-Wide Association Studies Revealed Several Candidate Genes of Meat Productivity in Saryarka Fat-Tailed Coarse-Wool Sheep Breed. Genes (Basel) 2024 Nov 29;15(12).
              doi: 10.3390/genes15121549pubmed: 39766815google scholar: lookup
            5. Timmer KB, Killian ML, Harley BAC. Paracrine signals influence patterns of fibrocartilage differentiation in a lyophilized gelatin hydrogel for applications in rotator cuff repair. Biomater Sci 2024 Sep 10;12(18):4806-4822.
              doi: 10.1039/d4bm00543kpubmed: 39150417google scholar: lookup
            6. Zamboulis DE, Marr N, Lenzi L, Birch HL, Screen HRC, Clegg PD, Thorpe CT. The Interfascicular Matrix of Energy Storing Tendons Houses Heterogenous Cell Populations Disproportionately Affected by Aging. Aging Dis 2024 Feb 1;15(1):295-310.
              doi: 10.14336/AD.2023.0425-1pubmed: 37307816google scholar: lookup