Mechanical induction of interleukin-11 regulates osteoblastic/cementoblastic differentiation of human periodontal ligament stem/progenitor cells

J Periodontal Res. 2015 Apr;50(2):231-9. doi: 10.1111/jre.12200. Epub 2014 Jun 20.

Abstract

Background and objective: The periodontal ligament (PDL) is continually exposed to mechanical loading caused by mastication or occlusion. Physiological loading is thus considered a key regulator of PDL tissue homeostasis; however, it remains unclear how this occurs. We recently reported that an appropriate magnitude of mechanical stretch can maintain PDL tissue homeostasis via the renin-angiotensin system. In the present study, we investigated the expression of interleukin-11 (IL-11) in human primary PDL cells (HPDLCs) exposed to stretch loading, the contribution of angiotensin II (Ang II) to this event and the effects of IL-11 on osteoblastic/cementoblastic differentiation of human PDL progenitor cells (cell line 1-17).

Material and methods: Human primary PDL cells, derived from human tissues, with or without antagonists against the Ang II receptors AT1 or AT2, were subjected to cyclical stretch loading with 8% elongation for 1 h. Expression of IL-11 was measured by ELISA in these cultures and by immunohistochemistry in the sectioned maxillae of rats. The osteoblastic/cementoblastic potential of cell line 1-17 was determined using cell proliferation, gene expression and Alizarin Red staining.

Results: Positive staining for IL-11 was observed in the PDL of rat maxillae and in cultures of HPDLCs. In HPDLCs exposed to stretch, expression of the IL11 gene and the IL-11 protein were up-regulated, concomitant with an increase in Ang II and via AT2. Recombinant human IL-11 (rhIL-11) stimulated an increase in expression of mRNA for the cementoblast-specific marker, CP-23, and for the osteoblastic markers, osteopontin and bone sialoprotein, and promoted proliferation in cell line 1-17. In addition, rhIL-11 also increased the degree of mineralized nodule formation in cell line 1-17 cultures treated with CaCl2 .

Conclusion: Mechanical loading appears to control proliferation and osteoblastic/cementoblastic differentiation of human PDL stem/progenitor cells through the regulation of Ang II and AT2 by IL-11.

Keywords: cytokines; periodontal ligament; periodontal maintenance; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin II / physiology
  • Angiotensin Receptor Antagonists / pharmacology
  • Animals
  • Biomechanical Phenomena
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Dental Cementum / physiology*
  • Female
  • Humans
  • Integrin-Binding Sialoprotein / analysis
  • Interleukin-11 / physiology*
  • Male
  • Mechanotransduction, Cellular / physiology*
  • Osteoblasts / physiology*
  • Osteopontin / analysis
  • Periodontal Ligament / cytology*
  • Proteins / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 2 / drug effects
  • Stem Cells / physiology*
  • Stress, Mechanical
  • Time Factors
  • Young Adult

Substances

  • Angiotensin Receptor Antagonists
  • CEMP1 protein, human
  • IL11 protein, human
  • Integrin-Binding Sialoprotein
  • Interleukin-11
  • Proteins
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Osteopontin
  • Angiotensin II