Hyaluronan induces odontoblastic differentiation of dental pulp stem cells via CD44

Dental pulp cells have the capacity to differentiate into odontoblasts. Dental damage caused by oral cavities, periodontal disease, or mechanical trauma induces the formation of reparative dentin, a poorly organized mineralized matrix that serves as a protective barrier to the dental pulp [1].

Dental pulp stem cells (DPSCs) are present in human dental pulp, even in adult pulp, as clonogenic and highly proliferative cells obtained after enzymatic disaggregation [2]. These cells harbor the characteristics of plastic adherence and express stem cell markers such as CD29, CD90, CD44, and CD146 [2]. Additionally, DPSCs express transcription factors expressed by embryonic stem cells, including Oct-4, Sox-2 and Nanog [3, 4]. Numerous researchers have since shown that DPSCs retain the capacity for both self-renewal and multiple cell lineage differentiation [5, 6] and can be stimulated, under specific conditions, to differentiate into various cell types such as adipocytes, myoblasts, neurons, chondrocytes, odontoblasts and osteoblasts both in vitro and in vivo [7–9]. Animal studies have also revealed great potential for DPSCs in the repair and regeneration of various tissues, including bone [10], muscle [3] and teeth [11].

Odontoblasts, especially those in the root ends of immature teeth, express CD44, which is strongly expressed by cells undergoing mineralization, such as ameloblasts, odontoblasts and osteoblasts in calcifying areas [12]. CD44 functions as an adhesion molecule and is a broadly distributed type I transmembrane glycoprotein receptor for the glycosaminoglycan hyaluronan (HA) [13, 14]. However, the effects of HA stimulation of CD44 on DPSCs remain unknown. In this study, we investigated the effect of HA on DPSCs.