Effects of dietary fatty acids on MC3T3-E1 osteoblast-like cells: Cyclooxygenase expression, prostaglandin E2 synthesis, and expression of bone formation markers
Abstract
The purpose of these studies was to evaluate the effects of exogenous dietary fatty acids on osteoblast function using the MC3T3-E1 osteoblast-like cell line. The hypotheses for these experiments were: (1) decreasing levels of arachidonic acid (AA) in the cells through supplementation of the n-3 PUFA eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) would attenuate prostaglandin E2 (PGE2) production in times of cyclooxygenase-2 (COX-2) activity. (2) Attenuation of PGE2 production by EPA and DHA would increase the production of bone formation markers including alkaline phosphatase activity and collagen production. The AA-derived PGE 2 is a stimulator of bone resorption and may have an etiological role in the loss of bone mass associated with diseases such as osteoporosis and skeletal metastasis. Current pharmacological intervention may produce serious side effects in some individuals; therefore, dietary intervention may be more beneficial and economical. These results demonstrate that MC3T3-E1 cells exposed to exogenous fatty acids exhibit changes in fatty acid composition reflecting the supplemented fatty acid. In the case of AA and EPA, supplementation with one decreased levels of the other. In addition, DHA reduced the level of AA. These fatty acids did not affect cell number or oxidative susceptibility of the membrane at concentrations up to 200 μM of the supplemented fatty acid. EPA and DHA led to decreases in PGE2 production in a competitive manner with AA and attenuated increased COX-2 protein expression in AA-treated cells under some experimental conditions. Collagen production was augmented in response to increasing concentrations of fatty acids. EPA and DHA tended to increase alkaline phosphatase activity when compared to AA treated cells. Cellular responses to fatty acids may depend on the maturation of the cell since osteoprotegerin, which inhibits osteoclastogenesis, was modulated by the fatty acid treatments at different culturing times. The results obtained in these experiments support other findings in which animals fed diets with a low ratio of n-6:n-3 fatty acids exhibited decreased ex vivo PGE2 production and enhancement of some markers of bone formation. Therefore, dietary intervention based on decreasing the ratio of n-6:n-3 fatty acids in the diet may diminish the bone loss observed during osteoporosis and skeletal metastasis by moderating PGE2 production.
Degree
Ph.D.
Advisors
Watkins, Purdue University.
Subject Area
Molecular biology|Nutrition
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