title: Decreased AP-1 activity and interleukin-11 expression by bone marrow stromal cells may be associated with impaired bone formation in aged mice.
abstract: Expression of an osteogenic cytokine, IL-11, is decreased in SAMP6. We show here that IL-11 transcription largely depends on AP-1 transcription factors, activities of which are decreased in SAMP6 as well as aged ICR mice. Therefore, diminished AP-1 activity and the resultant decline in IL-11 expression may play a role in impaired bone formation in the aged.
  
  
  BACKGROUND
  Evidence suggests that impaired osteoblastogenesis contributes to aging-associated osteopenia. The P6 strain of senescence-accelerated mice (SAM) is an animal model of senile osteoporosis, which exhibits low bone mass caused by impaired bone formation. Bone marrow stromal cells from SAMP6 show decreased osteoblastogenesis and increased adipogenesis. We previously demonstrated that these abnormalities of SAMP6 stromal cells may be attributed to decreased expression of interleukin (IL)-11.
  
  
  METHODS
  In this study, we attempted to determine the molecular mechanism of decreased IL-11 expression by SAMP6 stromal cells by cloning and analyzing the mouse IL-11 gene promoter.
  
  
  CONCLUSIONS
  We found that two tandem activating protein-1 (AP-1) sites that reside immediately upstream of TATA box play critical roles in IL-11 gene transcription. Gel shift analysis showed that binding activity to the IL-11 AP-1 sites was reduced in SAMP6 stromal cell nuclear extracts. Among multiple components of AP-1 transcription factors, Jun D binding was particularly decreased. Furthermore, decreased Jun D binding and IL-11 expression by stromal cells was also observed in aged mice of the ICR strain. Therefore, decreased AP-1 activity and a resultant decline in IL-11 expression by bone marrow stromal cells may play a role in impaired bone formation in the aged.
authors.affiliation: Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Tohjima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Inoue
authors.forename: Nobuchika
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kido
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ito
authors.forename: Shuji
authors.initials: S
authors.lastname: Kato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010012:Osteogenesis / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017154:Stromal Cells / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D017370:Interleukin-11; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1