title: Mechanical induction of interleukin-11 regulates osteoblastic/cementoblastic differentiation of human periodontal ligament stem/progenitor cells.
abstract: 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).
  
  
  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 .
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Oral Rehabilitation, Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Monnouchi
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: A
authors.initials: A
authors.lastname: Yuda
authors.forename: S
authors.initials: S
authors.lastname: Hamano
authors.forename: N
authors.initials: N
authors.lastname: Wada
authors.forename: A
authors.initials: A
authors.lastname: Tomokiyo
authors.forename: K
authors.initials: K
authors.lastname: Koori
authors.forename: H
authors.initials: H
authors.lastname: Sugii
authors.forename: S
authors.initials: S
authors.lastname: Serita
authors.forename: A
authors.initials: A
authors.lastname: Akamine
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D003739:Dental Cementum / Q000502:physiology*; D005260:Female; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000032:analysis; D017370:Interleukin-11 / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology*; D053495:Osteopontin / Q000032:analysis; D010513:Periodontal Ligament / Q000166:cytology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects; D013234:Stem Cells / Q000502:physiology*; D013314:Stress, Mechanical; D013997:Time Factors; D055815:Young Adult
chemical_list: D057911:Angiotensin Receptor Antagonists; C510886:CEMP1 protein, human; C508611:IL11 protein, human; D058574:Integrin-Binding Sialoprotein; D017370:Interleukin-11; D011506:Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D053495:Osteopontin; D000804:Angiotensin II
keywords: cytokines; periodontal ligament; periodontal maintenance; stem cells