MMP3 Contributes to Development of Periapical Lesions and Healing Response

Objective: Chronic inflammatory diseases of tooth-supporting structures are one of the most significant causes of tooth loss in adults and the most prevalent form of bone pathology in humans. We suspect that genetic variation in genes involved in bone remodeling, saliva function, immune responses, and dental development contribute to the level of bone destruction and remodeling and formation of more extensive periapical lesions in teeth affected by deep carious lesions.

Method: Sixteen hundred radiographic records in the Dental Registry and DNA Repository (DRDR) were screened for subjects with deep carious lesions with or without periapical lesions (≥3mm). DNA samples of patients with deep carious lesions in dentin were sorted into two groups: 158 cases with deep carious lesions but no periapical lesions, and 110 cases with periapical lesions and deep carious lesions.  Specific genes evaluated include genes that encode for the proteins of the matrix metalloproteinase complex (MMP2, MMP3, and MMP9), which contribute to connective tissue synthesis, breakdown and remodeling, as well as regulatory genes, such as the CR2, TIMP1, and TIMP2. Fifteen SNP markers in the six genes were selected. Genotypes were generated by end-point analysis in a Real Time PCR machine. Chi-square and Fisher’s exact tests were used to compare the frequencies of alleles and genotypes between cases.

Result: The MMP3 gene showed statistically significant variation at the rs639752 (p = 0.03) and rs679620 (p = 0.004) SNPs.

Conclusion: Variation in MMP3 is associated with periapical lesion formation due to untreated deep carious lesions and may contribute to varying levels of bone remodeling, regeneration, and inflammation in response to deep carious lesions, which could help predict host susceptibility to developing periapical lesions and healing response.