Impairment of osteoblast differentiation due to proliferation-independent telomere dysfunction in mouse models of accelerated aging

Haitao Wang, Qijun Chen, Seoung Hoon Lee, Yongwon Choi, Frederick Brad Johnson, Robert Pignolo

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We undertook genetic and nongenetic approaches to investigate the relationship between telomere maintenance and osteoblast differentiation, as well as to uncover a possible link between a known mediator of cellular aging and senile bone loss. Using mouse models of disrupted telomere maintenance molecules, including mutants in the Werner helicase (Wrn -/-), telomerase (Terc -/-), and Wrn -/- Terc -/- double mutants predisposed to accelerated bone loss, we measured telomere dysfunction-induced foci (TIFs) and markers of osteoblast differentiation in mesenchymal progenitor cells (MPCs). We found that telomere maintenance is directly and significantly related to osteoblast differentiation, with dysfunctional telomeres associated with impaired differentiation independent of proliferation state. Telomere-mediated defects in osteoblast differentiation are associated with increased p53/p21 expression and concomitant reduction in RUNX2. Conversely, MPCs from p53 -/- mice do not have substantial telomere dysfunction and spontaneously differentiate into osteoblasts. These results suggest that critical telomere dysfunction may be a prominent mechanism for age-related osteoporosis and limits MPC differentiation into bone-forming cells via the p53/p21 pathway.

Original languageEnglish (US)
Pages (from-to)704-713
Number of pages10
JournalAging Cell
Volume11
Issue number4
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Fingerprint

Telomere
Osteoblasts
Mesenchymal Stromal Cells
Maintenance
Bone and Bones
Cell Aging
Telomerase
Differentiation Antigens
Osteoporosis
Cell Differentiation

Keywords

  • Aging
  • Mesenchymal stem cells
  • Osteoporosis
  • Telomere
  • Telomere dysfunction

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Impairment of osteoblast differentiation due to proliferation-independent telomere dysfunction in mouse models of accelerated aging. / Wang, Haitao; Chen, Qijun; Lee, Seoung Hoon; Choi, Yongwon; Brad Johnson, Frederick; Pignolo, Robert.

In: Aging Cell, Vol. 11, No. 4, 01.08.2012, p. 704-713.

Research output: Contribution to journalArticle

Wang, Haitao ; Chen, Qijun ; Lee, Seoung Hoon ; Choi, Yongwon ; Brad Johnson, Frederick ; Pignolo, Robert. / Impairment of osteoblast differentiation due to proliferation-independent telomere dysfunction in mouse models of accelerated aging. In: Aging Cell. 2012 ; Vol. 11, No. 4. pp. 704-713.
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