Cell and Tissue Research

, Volume 325, Issue 3, pp 513–522 | Cite as

Elevated gene expression of MMP-1, MMP-10, and TIMP-1 reveal changes of molecules involved in turn-over of extracellular matrix in cyclosporine-induced gingival overgrowth

  • Bettina Dannewitz
  • Christina Edrich
  • Pascal Tomakidi
  • Annette Kohl
  • Olaf Gabbert
  • Peter Eickholz
  • Thorsten Steinberg
Regular Article


In humans, pathogenesis in cyclosporine A (CsA)-induced gingival overgrowth (GO) includes the accumulation of extracellular matrix (ECM) constituents, viz., collagen type-1 and type-3 and proteoglycans, in subgingival connective tissue. However, whether this increase is associated with alterations of molecules pivotal for the turn-over of collagens and proteoglycans remains unclear. The present study explores the status of matrix metalloproteinase MMP-1 and MMP-10, which are important for fibrillar collagen and proteoglycan turn-over, and their tissue inhibitor TIMP-1, on their gene expression and protein levels in frozen sections derived from GO and matched normal tissue. In situ hybridization (ISH) revealed elevated levels of MMP-1 gene expression in the connective tissue of GO compared with normal tissue. This elevation also applied to MMP-10 and TIMP-1, the latter exhibiting the strongest gene transcription in the deep connective tissue. These differences detected by ISH were corroborated by quantitative reverse transcription/polymerase chain reaction; relative gene expression analysis indicated a 1.9-fold increase for MMP-1, a 2.3-fold increase for MMP-10, and a 4.8-fold increase for TIMP-1. Detection of the protein by indirect immunofluorescence showed that normal gingival tissue was devoid of all three proteins, although they were detectable in GO tissue, with emphasis on TIMP-1. Analysis of our data indicates elevated levels of MMP-1 and-10, and particularly TIMP-1. With respect to TIMP-1, this elevation may in turn lead to alterations in ECM turn-over by abrogating MMP-1 and MMP-10, thereby contributing to ECM accumulation associated with GO.


Gingival overgrowth Cyclosporine A MMP-1 MMP-10 TIMP-1 Human 


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Bettina Dannewitz
    • 1
  • Christina Edrich
    • 2
  • Pascal Tomakidi
    • 2
  • Annette Kohl
    • 2
  • Olaf Gabbert
    • 3
  • Peter Eickholz
    • 4
  • Thorsten Steinberg
    • 2
  1. 1.Section of Periodontology, Department of Operative Dentistry and Periodontology, Dental SchoolUniversity of HeidelbergHeidelbergGermany
  2. 2.Department of Orthodontics and Dentofacial Orthopaedics, Dental SchoolUniversity of HeidelbergHeidelbergGermany
  3. 3.Department of Prosthodontics, Dental SchoolUniversity of HeidelbergHeidelbergGermany
  4. 4.Department of Periodontology, Center for Dental, Oral, and Maxillofacial MedicineUniversity Hospital FrankfurtFrankfurtGermany

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