The effect of donor age on the sensitivity of osteoblasts to the proliferative effects of TGF β and 1,25(OH 2) vitamin D 3

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 TGF β1 and 1,25-dihydroxy vitamin D 3 (1,25-D 3) 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-D 3 or TGF β1 or with vehicle. Cells from young rat bone, when treated with 1, 25-D 3, 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-D 3 treatment. A similar pattern of response to TGF β1 was found. When treated with 10 −9 M TGF β1, the rate of proliferation increased for young rat osteoblasts, but the old rat derived cells were unresponsive. The 10 −12 M dose of TGF β1 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 TGF β, two of the major controlling factors of skeletal development and maintenance.