Chronic periodontal disease is an infectious disease resulting in inflammation within the supporting tissue of the tooth, with progressive attachment and bone loss. It is characterized by pocket formation and/or gingival recession [1]. Some 5% to 20% of any population suffers from severe, generalized periodontitis; mild to moderate periodontitis affects a majority of adults and represents the main cause of tooth loss [2]. Along with dental caries, periodontal disease is the main cause of tooth loss; the teeth most commonly lost due to periodontal problems are the first and the second molars in the maxilla [3]. As result of tooth loss, the alveolar process undergoes bone resorption, causing a reduction of the amount of available bone for the insertion of dental implants and the achievement of prosthetic rehabilitation [4, 5].

Guided bone regeneration (GBR) procedures have become a common and safe treatment in dentistry, and autografts are considered the gold standard in GBR procedures for their osteogenic and osteoinductive properties. However, the principal limits are that a donor site is required and only a limited amount of graft is often recoverable [68]. For this reason, autologous mesenchymal stem cells (MSCs) would represent the ideal solution for stem cell-based bone tissue engineering.

Tissue engineering (TE) and regenerative medicine (RM) are emerging fields, focused on the development of alternative strategies for tissue or organ repair, that have made significant progress in the last years [9, 10]. TE provides new regenerated tissues by the appliance of cells, scaffold, and growth factors, alone or in combination; nowadays RM has made exceptional progress leading to the regeneration of numerous organs and organ systems by using the capability of stem cells to differentiate into specialized cell types [1113].

In adult humans stem cells are hosted in niches, a microenvironment that includes cellular and noncellular components that interact with each other to control the adult stem cells delegated to maintain the integrity of the tissues [14]. MSCs, defined as a population of nonhematopoietic fibroblast-like cells, able to differentiate into multiple lineages, including osteoblasts, adipocytes, and chondrocytes [9, 15]. During aging, the number of stem cell niches decreases, limiting the possibility of recognizing new sites for the collection of samples and obtaining multiple lines of differentiation for tissue engineering [14, 16, 17].

Over the last years, many niches have been described in the oral cavity: the dental pulp from permanent or deciduous teeth, the periodontal ligament, the apical papilla, the dental follicle, and the gingival tissue [1822].

Recently, oral MSCs have also been harvested from dental tissue that is not healthy, such as fractured teeth and teeth affected by caries or irreversible pulpitis or aggressive periodontitis [2326]. Dental pulp MSCs (DPSCs) and gingival MSCs (GMSCs) are clonogenic cells capable of both self-renewal and multiple lines of differentiation; moreover, compared to the bone marrow MSCs (BM-MSCs), DPSCs and GMSCs demonstrate the ability to proliferate faster, to be mostly homogenous, and to have excellent capacity to differentiate into osteogenic cells [18, 2729]. It is controversial, however, whether proinflammatory cytokines could compromise multipotency and regenerative potential in several types of MSCs in vitro. There is growing evidence that proinflammatory cytokines such as interleukin (IL)-1β or tumor necrosis factor (TNF)-α are important causal factors of cellular proliferation and differentiation in human MSCs [26, 3033]. Recently, some studies have focused on a possible link between proinflammatory cytokines, bone formation, and various heat shock proteins (HSPs). Inflammation and hypoxic conditions induce the expression of several HSPs engaged in protein folding and actin cytoskeletal organization [3436]. The actin polymerization remodeling is a fundamental process during lineage-specific differentiation; in this context, Chen et al. showed that the inhibition of main actin depolymerizing factors (ADFs) enhance osteoblastic differentiation in human stromal stem cells [36].

In this study, we evaluated the inflammatory effects on human dental stem cells, particularly DPSCs and GMSCs from inflamed dental tissue, and we investigated if they can be used both as an MSC source and as host tissue in regenerative therapies. We compared the MSC markers, MSC gene profile, proliferation, and in vitro differentiation ability of the DPSCs and GMSCs harvested from periodontally compromised teeth compared to healthy teeth. We investigated if the proinflammatory microenvironment negatively affects dental MSC characteristics and properties, and we speculated about a closer link between chronic inflammation and bone formation through the involvement of several HSPs and ADFs.