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Effects of short-term inflammatory and/or hypoxic pretreatments on periodontal ligament stem cells: in vitro and in vivo studies

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Abstract

In this study, we extensively screened the in vitro and in vivo effects of PDLSCs following short-term inflammatory and/or hypoxic pretreatments. We found that the 24-h hypoxic pretreatment of PDLSCs significantly enhanced cell migration and improved cell surface CXCR4 expression. In addition, hypoxia-pretreated PDLSCs exhibited improved cell colony formation and proliferation. Cells that were dually stimulated also formed more colonies compared to untreated cells but their proliferation did not increase. Importantly, the hypoxic pretreatment of PDLSCs enhanced cell differentiation as determined by elevated RUNX-2 and ALP protein expression. In this context, the inflammatory stimulus impaired cell OCN protein expression, while dual stimuli led to decreased RUNX-2 and OCN mRNA levels. Although preconditioning PDLSCs with inflammatory and/or hypoxic pretreatments resulted in no differences in the production of matrix proteins, hypoxic pretreatment led to the generation of thicker cell sheets; the inflammatory stimulus weakened the ability of cells to form sheets. All the resultant cell sheets exhibited clear bone regeneration following ectopic transplantation as well as in periodontal defect models; the amount of new bone formed by hypoxia-preconditioned cells was significantly greater than that formed by inflammatory stimulus- or dual-stimuli-treated cells or by nonpreconditioned cells. The regeneration of new cementum and periodontal ligaments was only identified in the hypoxia-stimulus and no-stimulus cell groups. Our findings suggest that PDLSCs that undergo short-term hypoxic pretreatment show improved cellular behavior in vitro and enhanced regenerative potential in vivo. The preconditioning of PDLSCs via combined treatments or an inflammatory stimulus requires further investigation.

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    1. State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 145th West Changle Road, Xi’an, Shaanxi, China

      Yang Yu, Chun-Sheng Bi, Rui-Xin Wu, Yuan Yin, Xi-Yu Zhang & Fa-Ming Chen

    2. National Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi’an, China

      Yang Yu, Chun-Sheng Bi, Rui-Xin Wu, Yuan Yin, Xi-Yu Zhang & Fa-Ming Chen

    3. Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, China

      Ping-Heng Lan

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    This work was supported by the National Natural Science Foundation of China (No. 81530050, 81471791 and 81500853) and the Program for New Century Excellent Talents in University (NCET-12-1005).

    Yang Yu, Chun-Sheng Bi and Rui-Xin Wu contributed equally to this work.

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    Yu, Y., Bi, CS., Wu, RX. et al. Effects of short-term inflammatory and/or hypoxic pretreatments on periodontal ligament stem cells: in vitro and in vivo studies. Cell Tissue Res 366, 311–328 (2016). https://doi.org/10.1007/s00441-016-2437-3

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