Scientific article| Volume 34, ISSUE 3, P495-503, March 2009

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In Vitro Flexor Tendon Cell Response to TGF-β1: A Gene Expression Study

  • B.R. Klass
    Corresponding author: B. R. Klass, MBBS, Department of Plastic and Reconstructive Surgery, Second Floor, Harrison House, The Royal London Hospital, Whitechapel, London E1 1BB, UK
    Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London; and the RAFT Institute, The Leopold Muller Building, Mount Vernon Hospital, Northwood, Middlesex, UK
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  • K.J. Rolfe
    Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London; and the RAFT Institute, The Leopold Muller Building, Mount Vernon Hospital, Northwood, Middlesex, UK
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  • A.O. Grobbelaar
    Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London; and the RAFT Institute, The Leopold Muller Building, Mount Vernon Hospital, Northwood, Middlesex, UK
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      Adhesion formation around zone II flexor tendon repairs remains an important clinical challenge. Tendon healing is complex, and when uncontrolled it may lead to adhesion formation. Transforming growth factor-β1 (TGF-β1) is a multipotent growth factor known to be involved in wound healing and scar formation. It has also been shown to have a role in both tendon healing and adhesion formation.


      Uninjured rabbit flexor tendons were divided into endotenon, epitenon, and sheath cells and cultured separately. The in vitro effect of TGF-β1 gene expression was determined on quiescent tendon cells using real-time polymerase chain reaction for collagen type 1, collagen type 3, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA).


      Endotenon-derived cells showed a statistically significant down-regulation of collagen type I gene expression in response to TGF-β1 compared with untreated endotenon cells and with both epitenon and sheath cells at a number of time points. However, endotenon cells showed an increase in collagen type 3 gene expression compared with untreated cells and epitenon cells. All cells showed a statistically significant increase in fibronectin in the later time points compared with the untreated cells. Endotenon-derived cells showed an early increase in PAI-1, whereas sheath cells showed a later increase.


      We have shown that cells cultured from 3 separate parts of the flexor tendon–sheath complex respond in different ways when stimulated with TGF-β1. The down-regulation of collagen types 1 and 3 in endotenon cells may give further insight into the effects of TGF-β1 in tendon healing. Also, the upregulation of fibronectin and PAI-1, combined with a down-regulation of tissue plasminogen activator, could explain the association of TGF-β1 with tendon adhesion formation. Treatments aimed at improving tendon healing and the prevention of adhesions may arise from modification of the effects of TGF-β1.

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