Sclerostin Deficiency Promotes Reparative Dentinogenesis

Abstract

In humans, the SOST gene encodes sclerostin, an inhibitor of bone growth and remodeling, which also negatively regulates the bone repair process. Sclerostin has also been implicated in tooth formation, but its potential role in pulp healing remains unknown. The aim of this study was to explore the role of sclerostin in reparative dentinogenesis using Sost knockout mice ( Sost). The pulps of the first maxillary molars were mechanically exposed in 3-mo-old Sost and wild-type (WT) mice ( n = 14 mice per group), capped with mineral trioxide aggregate cement, and the cavities were filled with a bonded composite resin. Reparative dentinogenesis was dynamically followed up by micro-computed tomography and characterized by histological analyses. Presurgical analysis revealed a significantly lower pulp volume in Sost mice compared with WT. At 30 and 49 d postsurgery, a large-forming reparative mineralized bridge, associated with osteopontin-positive mineralization foci, was observed in the Sost pulps, whereas a much smaller bridge was detected in WT. At the longer time points, the bridge, which was associated with dentin sialoprotein-positive cells, had expanded in both groups but remained significantly larger in Sost pulps. Sclerostin expression in the healing WT pulps was detected in the cells neighboring the forming dentin bridge. In vitro, mineralization induced by Sost dental pulp cells (DPCs) was also dramatically enhanced when compared with WT DPCs. These observations were associated with an increased Sost expression in WT cells. Taken together, our data show that sclerostin deficiency hastened reparative dentinogenesis after pulp injury, suggesting that the inhibition of sclerostin may constitute a promising therapeutic strategy for improving the healing of damaged pulps.

Sclerostin promotes human dental pulp cells senescence

“…Similar to the higher level of sclerostin in aged individuals, the expression level of sclerostin varies in embryonic and adult mouse incisors and molars ( Naka & Yokose, 2011 ), indicating a possible role of sclerostin in DPC senescence. Additionally, Collignon et al (2017) found that sclerostin deficiency increased reparative dentinogenesis in mice, implying anti-sclerostin might reverse the decreased regenerative potential of aged dental pulp. Taken together, we hypothesized a possible correlation between sclerostin and DPC senescence.…”

The role of sclerostin and dickkopf-1 in oral tissues – A review from the perspective of the dental disciplines

“…These findings are related to an increased SOST expression in wild type cells. Further more these results show that SOST deficiency accelerates reparative dentinogenesis after pulp damage and therefore inhibition of SOST may provide a promising therapeutic strategy to improve the healing of injured pulps ( Collignon et al ., 2017).…”

“…The odontoblasts which are involved in this repair process are clearly responsive to Wnt ( Zhao et al ., 2018). SOST knockout mice demonstrate dramatically enhanced formation of reparative mineralized bridges and increased mineralization in dental pulp cells compared with wild-type mice ( Collignon et al ., 2017). These findings are related to an increased SOST expression in wild type cells.…”

Acellular biomaterial strategies for endodontic regeneration

“…Recent reports of FOXQ1 and SOST affecting proliferation and mineralisation ability of DPSCs (respectively) open the door to delivery of micro or small interfering RNA molecules to regulate the expression of these genes. 81,82 Successful delivery of these molecules can be achieved incorporating appropriate carriers, cleavable links or via electrostatic interactions. The scaffolds and materials included in this review have potential to support the growth of dental tissues, but in endodontic regeneration, sealing materials are still required to isolate the pulp chamber from the oral cavity while regeneration occurs.…”