Purpose
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.
Methods
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).
Results
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.
Conclusions
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.
Key words
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References
- Tending tender tendons.Science. 2002; 295: 1011
- Factors influencing flexor tendon adhesions.Hand Clin. 1985; 1: 35-42
- Oral ibuprofen: evaluation of its effect on peritendinous adhesions and the breaking strength of a tenorrhaphy.J Hand Surg. 1986; 11A: 110-120
- Sodium hyaluronate as an adjunct in adhesion prevention after flexor tendon surgery in rabbits.J Hand Surg. 1992; 17A: 935-941
- Modulation of the formation of adhesions during the healing injured tendon.J Bone Joint Surg. 2000; 82B: 1054-1058
- Fibrin sealant in prevention of flexor tendon adhesions: an experimental study in the rabbit.J Hand Surg. 1993; 18A: 68-75
- Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta 1 increases postoperative range of motion.Plast Reconstr Surg. 2000; 105: 148-155
- Flexor tendon healing and adhesion formation after Sterispon wrapping: a study in the rabbit.Injury. 1979; 10: 211-216
- Prevention of restrictive adhesions with expanded polytetrafluoroethylene diffusible membrane following flexor tendon repair: an experimental study in rabbits.J Hand Surg. 1998; 23A: 658-664
- Efficacy of ADCON-T/N after primary flexor repair in Zone II: a controlled clinical trial.J Hand Surg. 2003; 28B: 113-115
- Pulmonary fibrosis: cytokines in the balance.Eur Respir J. 1998; 11: 1218-1221
- Elevated expression of transforming growth factor beta and proteoglycan production in experimental glomerulonephritis: possible role in expansion of the mesangial extracellular matrix.J Clin Invest. 1990; 86: 453-462
- Transforming growth factor beta and the liver.Hepatology. 2001; 34: 859-867
- Gene expression of transforming growth factor beta-1 in rabbit zone II flexor tendon wound healing: evidence for dual mechanisms of repair.Plast Reconstr Surg. 1997; 100: 937-944
- Flexor tendon healing in vitro: effects of TGF-beta on tendon cell collagen production.J Hand Surg. 2002; 27A: 615-620
- Transforming growth factor beta in disease: the dark side of tissue repair.J Clin Invest. 1992; 90: 1-7
- Experimental manipulation of transforming growth factor beta isoforms significantly affects adhesion formation in a murine surgical model.Am J Pathol. 2005; 167: 1005-1019
- Differential expression of transforming growth factor beta receptors in a rabbit zone II flexor tendon wound healing model.Plast Reconstr Surg. 2001; 108: 1260-1267
- Global expression profiling of fibroblast responses to transforming growth factor beta1 reveals the induction of inhibitor of differentiation-1 and provides evidence of a smooth muscle cell phenotypic switching.Am J Pathol. 2003; 162: 533-546
- Identification of novel TGF beta/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach.J Biol Chem. 2001; 276: 17058-17062
- Transforming growth factor beta regulates the levels of different fibronectin isoforms in normal cultured fibroblasts.FEBS Lett. 1988; 228: 42-44
- The distribution of types I and III collagen and fibronectin in the healing equine tendon.Connect Tissue Res. 1984; 12: 211-227
- TGF-beta 1 induced PAI-1 gene expression requires MEK activity and cell to substrate adhesion.J Cell Sci. 2001; 114: 3905-3914
- Peritoneal healing and adhesion formation/reformation.Hum Reprod Update. 2001; 7: 556-566
- Plasma levels of t-PA and PAI-1 correlate with the formation of experimental post-surgical peritoneal adhesions.Mediators Inflamm. 2006; 4: 1-4
- Tissue markers as predictors of postoperative adhesions.Br J Surg. 1998; 85: 1549-1554
- Differential gene expression in response to transforming growth factor beta1 by fetal and postnatal dermal fibroblasts.Wound Repair Regen. 2007; 15: 897-906
- TGF- beta 1 reverses the effects of matrix anchorage on the gene expression of decorin and procollagen type I in tendon fibroblasts.Clin Orthop Relat Res. 2005; 431: 226-232
- Analysis of relative gene expression delta using real-time quantitative PCR and the 2–ΔΔCT method.Methods. 2001; 25: 402-408
- Effect of TGF-beta inducible early gene deficiency on flexor tendon healing.J Orthop Res. 2006; 24: 569-575
- Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath.J Hand Surg. 2006; 31A: 1279-1287
- Clinical implications of growth factors in flexor tendon wound healing.J Hand Surg. 2004; 29A: 551-563
- Antibody neutralization of TGF-beta enhances the deterioration of collagen fascicles in a tissue-cultured tendon matrix with ex vivo fibroblast infiltration.J Biomech. 2007; 40: 2184-2190
- Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts.Biochem J. 1987; 247: 597-604
- Collagen synthesis by human liver (myo)fibroblasts in culture: evidence for a regulatory role of IL-1 beta, IL-4, TGF beta and IFN gamma.J Hepatol. 1995; 23: 307-317
- Localization and phenotypical characterization of collagen producing cells in TGF-beta 1-induced renal interstitial fibrosis.Histochem Cell Biol. 2003; 119: 267-280
- The skeletal attachment of tendons-tendon “enthuses”.Comp Biochem Physiol A Mol Integr Physiol. 2002; 133: 931-945
- The structure and functional significance of variations in the connective tissue within muscle.Comp Biochem Physiol A Mol Integr Phsyiol. 2002; 133: 947-966
- Advances in the biology of zone II flexor tendon healing and adhesion formation.Ann Plast Surg. 2000; 45: 83-92
- Genetic expression for type I procollagen in the early stages of flexor tendon healing.J Hand Surg. 1992; 17A: 551-558
- Collagen synthesis during primate flexor tendon repair in vitro.J Orthop Res. 1990; 8: 13-20
- OPC 15161 suppresses the proliferation of Tenon's capsule fibroblasts and the production of type I collagen and fibronectin stimulated by TGF-beta1 in vitro.Curr Eye Res. 1998; 17: 933-940
- Fibronectin-associated transforming growth factor.J Cell Physiol. 1987; 131: 184-189
- The accumulation of inflammatory cells in synovial sheath and epitenon during adhesion formation in healing rat tendon.Clin Exp Immunol. 1993; 93: 108-114
- Production of transforming growth factor-beta by human T lymphocytes and its potential role in the regulation of T cell growth.J Exp Med. 1986; 163: 1037-1050
- Fibroblast chemotaxis after tendon repair.J Hand Surg. 1991; 16A: 686-693
- PPARgamma agonists prevent TGFbeta1/Smad3-signaling in human hepatic stellate cells.Biochem Biophys Res Commun. 2006; 350: 385-391
- Inhibition of postsurgical adhesions in a standardized rabbit model: intraperitoneal treatment with tissue plasminogen activator.Int J Fertil. 1991; 36: 172-177
- Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model.Fertil Steril. 1989; 51: 509-512
- Reduction of experimental adhesion formation by inhibition of plasminogen activator inhibitor type 1.Br J Surg. 2001; 88: 286-289
- The early stages of flexor tendon healing: a morphologic study of the first fourteen days.J Hand Surg. 1985; 10A: 776-784
Article info
Publication history
Accepted:
October 29,
2008
Received:
March 20,
2008
Footnotes
No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
Identification
Copyright
© 2009 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
