Have you ever been to the dentist and heard the words “You have a cavity”? If so, then you are probably aware of the sound of a screeching drill and the taste of dental cement.  For decades, cavities have been fixed by drilling the problematic tooth to remove the decay and subsequently, filling the pit with inorganic cements that are either calcium or silicon-based. While the aforementioned procedure has been common practice for years, a new biological mechanism has been discovered that may change your future dental visits.  In a recent publication in Nature, Vitor C.M. Neves and colleagues discuss the ways in which small molecules can be used to foster the natural growth of tooth minerals as an alternative to the conventional use of inorganic cements for tooth fillings.

When a tooth is subject to disease or trauma (which is commonly known as a “cavity”), the inner tissue of the tooth is exposed, triggering a natural repair mechanism within the tooth.  This repair mechanism involves activation of the Wnt/β-catenin signaling pathway, which leads to an increase in reparative dentine (an essential mineral in teeth).  The reparative dentine creates a protective coating around the tooth to reduce further damage. While the naturally-produced reparative dentine helps protect the tooth, it lacks the quantity needed to adequately fix large damaged areas. Therefore, Neves and colleagues devised a plan to augment the activation of the Wnt/β-cat signaling pathway in hopes that it would lead to increased formation of reparative dentine.

Neves and colleagues first drilled holes into the molar teeth of mice. Next, they took sponges (named “Kolspon”) and soaked them in solutions of glycogen synthase kinase 3 (GSK3) inhibitors.  These are small molecules that activate the Wnt/β-cat pathway.  The three inhibitors used included BIO, CHIR99021, and Tideglusib.  Each Kolspon sponge was soaked in only one of the three GSK3 inhibitors so that the effects of each inhibitor could be tested separately.  The soaked sponges were then placed inside the cavities of the mouse molars for four to six weeks.  A control was also tested in which a non-soaked sponge was inserted into a drilled mouse molar.  After the sponges were removed, mineral deposition was measured by obtaining 3D x-rays with a micro-computed tomographic scanner.  Furthermore, mineralization due to treatment with traditional dental cement (mineral trioxide aggregate) was measured and compared to the newly developed method.

According to the results from the micro-computed tomographic scanning, there was an increase in mineralization when any of the three GSK3 inhibitors were used. Specifically, the inhibitor-soaked sponges led to twice as much mineral formation in comparison to the control, and the inhibitor-soaked sponges led 1.7 times as much mineral formation in comparison to the traditional mineral trioxide aggregate (MTA) treatment. Furthermore, the use of the inhibitor-soaked sponges resulted in the formation of more reparative dentine than both the control and the MTA. After six weeks of treatment, the teeth that were treated with the inhibitor-soaked sponges were completely filled.  The experiments also showed that there were no remnants of the Kolspon sponges in the locations of dentine formation; the naturally growing minerals took the place of the sponges, successfully filling the cavity without leaving foreign material in the teeth. On the other hand, the cavities that were filled with traditional materials (such as MTA) will contain unnatural material forever.

Based on the work of Neves and colleagues, the scientific and medical communities have obtained more information regarding dentine repair.  Due to the success of the GSK3 inhibitors, Neves and colleagues have discovered an alternative, more natural mechanism for tooth restoration.  According to the researchers, the mineral volume of the tooth is never fully restored when traditional materials (such as MTA) are used to fill the tooth.  Therefore, the use of GSK3 inhibitors may become a more popular and ideal option due to their ability to promote natural repair mechanisms that could lead to natural mineral volumes. In order to gain more insight on the use of GSK3 inhibitors to restore tooth damage, clinical trials should be carried out. If successful, the future of dentistry could be changed forever.  


  1. Neves, V. C., Babb, R., Chandrasekaran, D., & Sharpe, P. T. (2017, January 09). Promotion of natural tooth repair by small molecule GSK3 antagonists. Retrieved from http://www.nature.com/articles/srep39654

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