Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring.
Epidemiological studies suggest that environmental influences such as maternal nutrition, programme skeletal growth during intrauterine and early postnatal life. However, the mechanism whereby the skeletal growth trajectory is modified remains unclear. We have addressed this using a rat model of mat...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1797059182345584640 |
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| author | Oreffo, R Lashbrooke, B Roach, H Clarke, N Cooper, C |
| author_facet | Oreffo, R Lashbrooke, B Roach, H Clarke, N Cooper, C |
| author_sort | Oreffo, R |
| collection | OXFORD |
| description | Epidemiological studies suggest that environmental influences such as maternal nutrition, programme skeletal growth during intrauterine and early postnatal life. However, the mechanism whereby the skeletal growth trajectory is modified remains unclear. We have addressed this using a rat model of maternal protein insufficiency to investigate the cellular mechanisms involved in the programming of bone development. The aims of this study were to determine whether colony formation (colony forming unit-fibroblastic, CFU-F), proliferation, and differentiation of bone marrow stromal cells from offspring of female rats maintained on normal (18% casein) or low (9% casein) protein was altered and, whether their responses to growth hormone (GH), 1,25(OH)(2)D3, and IGF-1 differed. Dams were fed an 18% casein (control) diet or 9% casein (low protein) diet from conception until the end of pregnancy. Offspring were then fed a normal protein diet until harvest at 8, 12, and 16 weeks after birth. At 8 weeks, total CFU-F and alkaline phosphatase-positive CFU-F were significantly (P < 0.01) reduced in the low protein group compared to controls. At 12 weeks, no significant differences were observed in colony formation. Modulation of osteoblast proliferation and differentiation by IGF-1 and GH was observed (P < 0.01) in the control group at 8 weeks and the low protein group at 12 weeks. Alkaline phosphatase specific activity was significantly decreased at 8 weeks (P < 0.001) in the low protein group. At 12 and 16 weeks this was reversed, with significantly increased specific activity in the low protein group. These results suggest that normal proliferation and differentiation of mesenchymal stem cells were delayed by maternal protein restriction during early life. Furthermore, these results suggest that, with skeletal maturity, "catch-up" or a physiological shift in bone cell activity was present in the low protein group. These alterations in mesenchymal stem cell function by the early environment may represent an important candidate mechanism for the programming of osteoporosis and associated consequences in later life. |
| first_indexed | 2024-03-06T20:00:34Z |
| format | Journal article |
| id | oxford-uuid:272644a5-e064-4134-af17-4bee7429962b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:00:34Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:272644a5-e064-4134-af17-4bee7429962b2022-03-26T12:05:10ZMaternal protein deficiency affects mesenchymal stem cell activity in the developing offspring.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:272644a5-e064-4134-af17-4bee7429962bEnglishSymplectic Elements at Oxford2003Oreffo, RLashbrooke, BRoach, HClarke, NCooper, CEpidemiological studies suggest that environmental influences such as maternal nutrition, programme skeletal growth during intrauterine and early postnatal life. However, the mechanism whereby the skeletal growth trajectory is modified remains unclear. We have addressed this using a rat model of maternal protein insufficiency to investigate the cellular mechanisms involved in the programming of bone development. The aims of this study were to determine whether colony formation (colony forming unit-fibroblastic, CFU-F), proliferation, and differentiation of bone marrow stromal cells from offspring of female rats maintained on normal (18% casein) or low (9% casein) protein was altered and, whether their responses to growth hormone (GH), 1,25(OH)(2)D3, and IGF-1 differed. Dams were fed an 18% casein (control) diet or 9% casein (low protein) diet from conception until the end of pregnancy. Offspring were then fed a normal protein diet until harvest at 8, 12, and 16 weeks after birth. At 8 weeks, total CFU-F and alkaline phosphatase-positive CFU-F were significantly (P < 0.01) reduced in the low protein group compared to controls. At 12 weeks, no significant differences were observed in colony formation. Modulation of osteoblast proliferation and differentiation by IGF-1 and GH was observed (P < 0.01) in the control group at 8 weeks and the low protein group at 12 weeks. Alkaline phosphatase specific activity was significantly decreased at 8 weeks (P < 0.001) in the low protein group. At 12 and 16 weeks this was reversed, with significantly increased specific activity in the low protein group. These results suggest that normal proliferation and differentiation of mesenchymal stem cells were delayed by maternal protein restriction during early life. Furthermore, these results suggest that, with skeletal maturity, "catch-up" or a physiological shift in bone cell activity was present in the low protein group. These alterations in mesenchymal stem cell function by the early environment may represent an important candidate mechanism for the programming of osteoporosis and associated consequences in later life. |
| spellingShingle | Oreffo, R Lashbrooke, B Roach, H Clarke, N Cooper, C Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring. |
| title | Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring. |
| title_full | Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring. |
| title_fullStr | Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring. |
| title_full_unstemmed | Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring. |
| title_short | Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring. |
| title_sort | maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring |
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