The effect of donor age on the sensitivity of osteoblasts to the proliferative effects of TGFβ and 1,25(OH2) vitamin D3

Matthew J. Shiels, Andrea M. Mastro, Carol V. Gay

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The loss of osteoblast function in aging bone is one of the major causes of osteopenia, or loss of bone mass. In this study, this loss of function was investigated by examining the proliferative response of rat long bone periosteal osteoblasts to TGFβ1 and 1,25-dihydroxy vitamin D3 (1,25-D3) as a function of donor age. Using a DNA binding fluorescent dye, DNA levels were measured in osteoblast cultures derived from either young adult (3-4 months) or old (14-15 months) rats following treatment with two concentrations (10-9 M or 10-12 M) of either 1,25-D3 or TGFβ1 or with vehicle. Cells from young rat bone, when treated with 1, 25-D3, showed a dose-dependent increase in proliferation when treated with the higher dose and a decrease in proliferation when treated with the lower dose. Osteoblasts isolated from old rats did not respond to 1, 25-D3 treatment. A similar pattern of response to TGFβ1 was found. When treated with 10-9 M TGFβ1, the rate of proliferation increased for young rat osteoblasts, but the old rat derived cells were unresponsive. The 10-12 M dose of TGFβ1 was ineffective for both young and old cells. This study has shown that osteoblasts derived from old donors are impaired in their ability to respond to vitamin D and TGFβ, two of the major controlling factors of skeletal development and maintenance.

Original languageEnglish (US)
Pages (from-to)2967-2975
Number of pages9
JournalLife Sciences
Volume70
Issue number25
DOIs
StatePublished - May 10 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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