The Comparison of the Differentiation Potential of Periodontal Ligament and Dental Pulp Mesenchymal Stem Cells in the Inflammatory Synovium Microenvironment

BACKGROUND/AIMS: Dental mesenchymal stem cells are easily accessible sources for mesenchymal stem cells (MSCs) and can rapidly proliferate in culture conditions. Rheumatoid arthritis (RA) is a chronic and multi-systemic autoimmune inflammatory disease that results in cartilage damage. The present study aimed to investigate the regenerative potential of dental MSCs in the synovial fluid microenvironment of patients with RA. MATERIALS AND METHODS: Synovial fluid samples (8-10 mL/patient) were collected from patients with RA (age; 48-67 years). Dental pulp (DP) and periodontal ligament (PL) tissues were collected from healthy individuals, and the tissues were enzymatically digested in 3 mg/mL collagenase type I. MSCs were cultured in Dulbecco's Modified Eagle Medium (DMEM). The cells were cultured in the presence and absence of the synovial fluid samples of the patients with RA and subjected to flow cytometry analysis for cell surface expressions of positive markers for chondrogenesis (CD49e) and an osteogenic marker (alkaline phosphatase; ALP). The differentiation capacity of MSCs was evaluated with osteogenic or chondrogenic stimulation media and analyzed by staining the cells with Alizarin Red or Alcian Blue, respectively. RESULTS: The cytokines interleukin (IL)-1 beta (61.1 +/- 9.8) and IL-6 (2386.7 +/- 397.4) were significantly higher in the end-stage RA-SF samples, compared to the early-stage RA-SF samples (IL-1 beta:35.2 +/- 4.8, IL-6:561.3 +/- 197.6) (p<0.05, p<0.001, respectively). DP-MSCs were significantly differentiated to osteocytes and formed calcium deposits cultured with end-stage RA-SF samples, whereas PL-MSCs were differentiated to osteocytes in limited levels, and low concentrations of calcium deposits were observed. Chondrocytes were observed in DP and PL-MSCs, and cartilage formation was observed only in DP-MSCs when cultured with end-stage RA-SF samples. The neutralization of IL-1 beta or IL-6 tended to decrease osteogenic marker expressions of DP-MSCs cultured in the presence of end-stage RA-SF samples. CONCLUSION: The present study showed the differentiation potential of DP-MSCs into osteogenic and chondrogenic lineage in the inflammatory microenvironment of SF. DP-MSCs may be candidates for tissue regeneration, especially in patients with RA with bone or cartilage erosions.

Automated summary

The study showed the regenerative potential of dental mesenchymal stem cells in the synovial fluid microenvironment of patients with rheumatoid arthritis, with differentiation into osteogenic and chondrogenic lineage. They may be candidates for tissue regeneration, especially in patients with RA with bone or cartilage erosions.