Article: The effect of donor age on the sensitivity of osteoblasts to the proliferative effects of TGF(beta) and 1,25(OH(2)) vitamin D(3).
2002 Volume 70, Issue 25, Page(s) 2967–2975
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( ... ...
| 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(beta1) 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(beta1) 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(beta1) was found. When treated with 10(-9) M TGF(beta1), the rate of proliferation increased for young rat osteoblasts, but the old rat derived cells were unresponsive. The 10(-12) M dose of TGF(beta1) 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(beta), two of the major controlling factors of skeletal development and maintenance. |
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| MeSH term(s) | Age Factors ; Animals ; Calcitriol/pharmacology ; Calcium Channel Agonists/pharmacology ; Cells, Cultured ; Collagen Type I/genetics ; Collagen Type I/metabolism ; DNA/metabolism ; Female ; Osteoblasts/cytology ; Osteoblasts/drug effects ; Osteoblasts/physiology ; Rats ; Rats, Inbred F344 ; Receptors, Parathyroid Hormone/genetics ; Receptors, Parathyroid Hormone/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta/pharmacology |
| Chemical Substances | Calcium Channel Agonists ; Collagen Type I ; Receptors, Parathyroid Hormone ; Transforming Growth Factor beta ; DNA (9007-49-2) ; Calcitriol (FXC9231JVH) |
| Language | English |
| Publishing date | 2002-05-10 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Research Support, U.S. Gov't, P.H.S. |
| ZDB-ID | 3378-9 |
| ISSN | 1879-0631 ; 0024-3205 |
| ISSN (online) | 1879-0631 |
| ISSN | 0024-3205 |
| DOI | 10.1016/s0024-3205(02)01548-5 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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