The iPLA2 and GPx enzyme activities of PRDX6 are associated with human dental pulp stem cell-based bone formation Kyung-Ran Park1, Hyung-Mun Yun2*, 1Department of Oral & Maxillofacial Regeneration, Graduate School, Kyung Hee University, Seoul 02453, Republic of Korea; 2Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02453, Republic of Korea *Corresponding Author
Peroxiredoxins (PRDXs) are thiol-specific antioxidant enzymes that regulate redox balance that are critical for maintaining the cellular potential for self-renewal and stemness. Stem cell-based regenerative medicine is a promising approach in tissue reconstruction. However, to obtain functional cells for use in clinical applications, stem cell technology still requires improvements. In the present study, we found that PRDX6 levels were decreased during osteogenic differentiation in human dental pulp stem cells (hDPSCs). hDPSCs stably expressing Myc-PRDX6 (hDPSC/myc-PRDX6) inhibited cell growth in hDPSCs during osteogenic differentiation and impaired osteogenic phenotypes such as alkaline phosphatase (ALP) activity, mineralized nodule formation, and osteogenic marker genes (ALP and OCN). hDPSC cell lines stably expressing mutant GPx (PRDX6(C47S)) and iPLA2 (PRDX6(S32A)) were also generated. Each mutant form of PRDX6 abolished the impaired osteogenic phenotypes, the TGF-mediated Smad2 and p38 pathways, and Runx2 expression. Further, in vivo experiments revealed that hDPSC/myc-PRDX6 suppressed hDPSC-based bone regeneration in calvarial defect mice, and newborn PRDX6 transgenic mice exhibited delayed bone development and reduced Runx2 expression. These findings illuminate the effects of PRDX6 during osteogenic differentiation of hDPSCs, and also suggest that regulating PRDX6 may improve the clinical utility of stem cell-based regenerative medicine for the treatment of bone diseases.
This work was supported by the National Research Foundation of Korea [NRF] grant funded by the Korea government (MSIP) (2015R1D1A1A01059240).
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