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Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring

Oreffo, Richard O.C., Lashbrooke, Benjamin, Roach, Helmtrud I., Clarke, Nicholas M. and Cooper, Cyrus (2003) Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring Bone, 33, (1), pp. 100-107. (doi:10.1016/S8756-3282(03)00166-2).

Record type: Article


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)2D3, 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.

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Published date: July 2003
Keywords: bone marrow, programming, maternal, in utero, protein, osteoprogenitor


Local EPrints ID: 25861
ISSN: 8756-3282
PURE UUID: 17bbd9a6-2e5c-4d30-aa5e-9a6057f3169f
ORCID for Richard O.C. Oreffo: ORCID iD
ORCID for Cyrus Cooper: ORCID iD

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Date deposited: 21 Apr 2006
Last modified: 17 Jul 2017 16:09

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Author: Benjamin Lashbrooke
Author: Helmtrud I. Roach
Author: Cyrus Cooper ORCID iD

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