Abstract
Vocal fold scarring remains a therapeutic challenge. Our research group has indicated that bone marrow-derived stromal cells (BSCs) may have therapeutic potential in restoration of injured vocal folds. However, it is still unclear how BSCs restore the viscoelasticity of vocal fold mucosa. Since a feature of vocal fold scarring is the disorganization of the extracellular matrix (ECM), it is important to understand how BSCs produce ECM. The present study aimed to clarify ECM gene expression in BSCs, and also examined the effects of hepatocyte growth factor (HGF) on this expression. BSCs obtained from the femurs of four Sprague−Dawley rats were cultured with or without HGF. The mRNA expression of ECM components (type I procollagen, decorin, Has2, CD44, MMP-1, and GAPDH) were examined in cultured BSCs and the vocal fold mucosa by the reverse transcription-polymerase chain reaction (RT-PCR). The mRNA expression of Has2 and MMP-1 was significantly stronger in BSCs than in the vocal folds (P < 0.05). Expression of Has2 in BSCs was significantly increased by the administration of HGF (P < 0.05). There was no significant difference in the gene expression of other ECM molecules between BSCs and vocal fold mucosa. Increased expression of Has2 and MMP-1 genes from BSCs may have a positive potential in the treatment of vocal fold scarring.
Similar content being viewed by others
References
Ford CN, Bless DM (1987) Collagen injection in the scarred vocal fold. J Voice 1:116–118
Staskowski PA, Ford CN, Inagi K (1998) The histologic fate of autologous collagen injected in the canine vocal fold. Otolaryngol Head Neck Surg 118:187–190
Kriesel KJ, Thibeault SL, Chan RW, Suzuki T, VanGroll PJ, Bless DM, Ford CN (2002) Treatment of vocal fold scarring: rheological and histological measures of homologous collagen matrix. Ann Otol Rhinol Laryngol 111:884–889
Brandenburg JH, Kirkham W, Koschkee D (1992) Vocal cord augmentation with autogenous fat. Laryngoscope 102:495–500
Garrett CG, Soto J, Riddick J, Billante CR, Reinisch L (2001) Effect of mitomycin-c on vocal fold healing in a canine model. Ann Otol Rhinol Laryngol 110:25–30
Thibeault SL, Gray SD, Bless DM, Chan RW, Ford CN (2002) Histologic and rheologic characterization of vocal fold scarring. J Voice 16:96–104
Thibeault SL, Bless DM, Gray SD (2003) Interstitial protein alterations in rabbit vocal fold with scar. J Voice 17(3):377–383
Gray SD, Titze IR, Chan R, Hammond TH (1999) Vocal fold proteoglycans and their influence on biomechanics. Laryngoscope 109:845–854
Savani R, Bagli DJ, Harrison RE, Turley EA (2000) The role of hyaluronan-receptor interactions in wound repair. In: Garg HG, Longaker MT (eds) Scarless wound healing. Marcel Dekker, New York pp 115–137
Matsumoto K, Nakamura T (1997) Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res C 239:639–644
Hirano S, Bless DM, Heisey D, Ford C (2003) Roles of hepatocyte growth factor and transforming growth factor beta1 in production of extracellular matrix by canine vocal fold fibroblasts. Laryngoscope 113(1):144–148
Hirano S, Bless DM, Nagai H, Rousseau B, Welham NV, Montequin DW, Ford CN (2004) Growth factor therapy for vocal fold scarring in canine model. Ann Otol Rhinol Laryngol 113:777–785
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49
Kanemaru S, Nakamura T, Omori K, Kojima H, Magrufov A, Hiratsuka Y, Hirano S, Ito J, Shimizu Y(2003) Regeneration of the vocal fold using autologous mesenchymal stem cells. Ann Otol Rhinol Laryngol 123:702–711
Kanemaru S, Nakamura T, Yamashita M, Yamashita M, Magrufov A, Kita T, Tamaki H, Tamura Y, Iguchi F, Kim TS, Kishimoto M, Omori K, Ito J (2005) Destiny of autologous bone marrow-derived stromal cells implanted in the vocal fold. Ann Otol Rhinol Laryngol 114(12):907–912
Gray SD, Tritle N, Li W (2003) The effect of mitomycin on extracellular matrix proteins in a rat wound model. Laryngoscope 113(2):237–242
Saavalainen K, Pasonen-Seppanen S, Dunlop TW, Tammi R, Tammi MI, Carlberg C (2005) The human hyaluronan synthase 2 gene is a primary retinoic acid and epidermal growth factor responding gene. J Biol Chem 280(15):14636–14644
Kihara Y, Tashiro M, Nakamura H, Yamaguchi T, Yoshikawa H, Otsuki M (2001) Role of TGF-beta1, extracellular matrix, and matrix metalloproteinase in the healing process of the pancreas after induction of acute necrotizing pancreatitis using arginine in rats. Pancreas 23(3):288–295
Hirano M (1995) Phonosurgery: past, present, and future. Trans Am Broncho-Esophagol Assoc 25–30
Langer R, Vacanti JP (1993) Tissue engineering. Science 260(5110):920–926. Review
Ozaki I, Zhao G, Mizuta T, Ogawa Y, Hara T, Kajihara S, Hisatomi A, Sakai T, Yamamoto K (2002) Hepatocyte growth factor induces collagenase (matrix metalloproteinase-1) via the transcription factor Ets-1 in human hepatic stellate cell line. J Hepatol 36:169–178
Dugan TA, Yang VW, McQuillan DJ, Höök M (2006) Decorin modulates fibrin assembly and structure. J Biol Chem 281(50):38208–38216
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ohno, T., Hirano, S., Kanemaru, Si. et al. Expression of extracellular matrix proteins in the vocal folds and bone marrow derived stromal cells of rats. Eur Arch Otorhinolaryngol 265, 669–674 (2008). https://doi.org/10.1007/s00405-007-0522-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00405-007-0522-7