Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo.

To evaluate the dentinogenetic effects of tissue inhibitor of metalloprotease (TIMP1) on human pulp cells in vitro and rat pulp tissue in vivo. The effect of TIMP1 on pulp cell functions related to hard tissue formation as part of the wound healing process (i.e. biocompatibility, proliferation, differentiation and mineralized nodule formation) was evaluated in vitro and using a direct pulp capping experimental animal model in vivo. The effects of different-sized cavity preparations on hard tissue formation induced by ProRoot MTA at 2 weeks were evaluated using micro-computed tomography (micro-CT). Tertiary dentine formation quality and quantity after pulp capping using TIMP1, ProRoot MTA and phosphate-buffered saline (PBS) was also evaluated after 4 weeks using micro-CT in term of dentine volume (DV), dentine mineral density (DVD) and histological analysis. The data were evaluated by Student's t-test, one-way ANOVA with Tukey's post hoc test, the Kruskal-Wallis test or the Steel-Dwass test. P values < 0.05 were considered statistically significant. TIMP1 significantly stimulated dental pulp stem cell proliferation, differentiation, and mineralization and was more biocompatible compared with the PBS control (P < 0.05). In the pulp capping model, the amount of tertiary dentine that formed was directly proportional to the size of the pulp exposure; greater amounts of tertiary dentine were observed in pulps with larger exposures after 2 weeks. 4-week samples of TIMP1 and ProRoot MTA had similar characteristics, but both sample significantly induced tertiary dentine formation beneath the cavity compared with PBS (P <  0.05) under standardized cavity preparations. TIMP1 has an important role in pulpal wound healing, which makes it a potential biological pulp capping material and candidate molecule for regenerative endodontic therapy.