MMP-7 and TIMP-1, New Targets in Predicting Poor Wound Healing in Apical Periodontitis

By Letra A, Ghaneh G, Zhao M, Ray H Jr, Francisconi CF, Garlet GP, Silva RM

Date: 01/2013
Journal: JOE


  • To investigate the expression of MMPs and TIMPs messenger RNA and protein levels in apical periodontitis lesions.


  • N= 15 (CAA), 18 (AAP)
  • Exclusion criteria: Patients w/medical conditions requiring the use of systemic modifiers of bone metabolism or other assisted drug therapy during the last 6 months before initiation of the study, patients with pre-existing conditions such as periodontal disease, and pregnant or lactating women.
  • Inclusion criteria: Patients with periapicalrarefaction characterized radiographically with the disappearance of the periodontal ligament space and discontinuity of the lamina dura(previous RCT).
  • Positive/negative control: Healthy periodontal ligament tissue samples (n = 10) obtained from premolars extracted for orthodontic purposes.
  • Control & Design: Biopsies collected at time of surgery and stored in 10% Formalin. Real-time PCR used in triplicate reactions, using specific primers for the various MMP’s and TIMP’s. Immunohistochemistry  immunocytochemistry, and cell culturing was also conducted on the samples.
  • Criteria of evaluation: Increased expression of MMP’s, TIMP’s.


  • Significantly higher mRNA levels found for all MMP, TIMP when compared to healthy samples.
  • Increased expression of MMP-2, 7, 9 in CAA cases
  • Increased expression of TIMP-1 in AAP cases
  • Expression of MMP-7 and TIMP-1 appear to congregate in the golgi apparatus
  • Expression of MMP’s, TIMP’s increased in LPS infected cells vs non-infected cells

Clinical Significance:

MMP 2,7,9 are more efficient at cleaving Type IV collagen – may be justified b/c in CAA, development of sinus tract requires degradation of ECM and BM to form. Up-regulation of TIMP-1 in AAP may be related to a protective effect against ECM degradation and bone resorption. MMP-7 and TIMP-1 are proposed as predictors of poor wound healing in apical periodontitis.