Biogerontology

, Volume 13, Issue 5, pp 467–478

Bone marrow stromal cells from aged male rats have delayed mineralization and reduced response to mechanical stimulation through nitric oxide and ERK1/2 signaling during osteogenic differentiation

  • Danese M. Joiner
  • Riyad J. Tayim
  • Allen Kadado
  • Steven A. Goldstein
Research Article

DOI: 10.1007/s10522-012-9391-6

Cite this article as:
Joiner, D.M., Tayim, R.J., Kadado, A. et al. Biogerontology (2012) 13: 467. doi:10.1007/s10522-012-9391-6

Abstract

Bone marrow stromal cells (MSCs) are a source of osteoblast precursors that can be recruited during bone remodeling or injury, both important processes in aging populations. With advancing age, alterations in bone structure and mineralization are often associated with an increase in osteoporosis and fracture risk. Changes in the number of osteoprogenitor cells and their osteogenic potential may occur with advancing age; however few studies have considered the influence of mechanical conditions. Here, we investigated the ability of bone MSCs from mature and aged rats to differentiate into osteoblasts and to respond to short and long periods of mechanical stimulation through signaling by ERK1/2, nitric oxide (NO), and prostaglandin E2 (PGE2) during differentiation. Mineralization was delayed and reduced, but extracellular matrix production appeared less affected by increased age. Differentiating MSCs from aged animals had a decreased response to short and long periods of mechanical stimulation through ERK1/2 signaling, and to long periods of mechanical loading through NO signaling early and late during differentiation. Increases in relative PGE2 signaling were higher in MSCs from aged animals, which could compensate for reduced ERK1/2 and NO signaling. The decreased mineralization may decrease the ability of cells from aged animals to respond to mechanical stimulation through ERK1/2 and NO signaling, with increased impairment over differentiation time. Decreasing the delay in mineralization of MSCs from aging animals might improve their ability to respond to mechanical stimulation during bone remodeling and injury, suggesting therapies for bone fragility diseases and tissue engineering treatments in elderly populations.

Keywords

AgeMarrow stromal cellMechanotransductionERK1/2Nitric oxideOsteoporosis

Supplementary material

10522_2012_9391_MOESM1_ESM.docx (900 kb)
Supplementary material 1 (DOCX 899 kb)

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Danese M. Joiner
    • 1
    • 2
  • Riyad J. Tayim
    • 1
  • Allen Kadado
    • 1
  • Steven A. Goldstein
    • 1
  1. 1.Orthopaedic Research Laboratories, Department of Orthopaedic SurgeryUniversity of MichiganAnn ArborUSA
  2. 2.Laboratory of Cell Signaling and CarcinogenesisVan Andel Research InstituteGrand RapidsUSA