Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Abstract

Abstract. Age-related bone loss eventually leads to osteopenia in men and women. The etiology of age-related bone loss is currently unknown; however, decreased osteoblast activity contributes to this phenomenon. In turn, osteoblast proliferation and function is dependent on energy production, thus the loss of energy production that occurs with age may account for the deficient osteoblast activity. Carnitine and dehydroepiandrosterone-sulfate (DHEAS), both of which decline with age, promote energy production through fatty acid metabolism. Thus, we hypothesized that carnitine and DHEAS would increase osteoblast activity in vitro. Accordingly, we measured the effect of carnitine and DHEAS on palmitic acid oxidation as a measure of energy production, and alkaline phosphatase (ALP) activity and collagen type I (COL) as indices of osteoblast function in primary porcine osteoblast-like cell cultures. Carnitine (10 −3 and 10 −1 M) but not DHEAS (10 −9 , 10 −8 , and 10 −7 M) increased carnitine levels within the cells. Carnitine alone and in combination with DHEAS increased palmitic acid oxidation. Both carnitine and DHEAS alone and in an additive fashion increased ALP activity and COL levels. These results demonstrate that in osteoblast-like cells in vitro, energy production can be increased by carnitine and osteoblast protein production can be increased by both carnitine and DHEAS. These data suggest that carnitine and DHEAS supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss. Key words:Osteoblast -Carnitine -Dehydroepiandrosterone sulfate -Alkaline phosphatase -Collagen Type I.Bone loss is often divided into two broad mechanisms: (1) postmenopausal bone loss, characterized by increased osteoclast activity, and (2) age-related bone loss, characterized by decreased osteoblast activity. Osteoblast activity is dependent on energy production. Thus, it is plausible that the loss of energy production, which accompanies age, may account for decreased osteoblast activity. Most cells use both glucose and fatty acid oxidation pathways for ATP synthesis, although some cell types show a substrate preference. For instance, some studies have suggested that glucose is the major fuel substrate for bone [1,2]. However, more recent work indicates that cell populations enriched with osteoblast-like cells generate 40-80% of the energy demands through fatty acid oxidation [3]. Osteoblasts are responsible for bone formation and it follows that they maintain a high rate of ATP utilization to support the requisite protein synthesis. Cells with a high rate of protein synthesis generate ATP from fatty acid oxidation, the most efficient metabolic process for energy production [4][5][6]. Thus, modulation of fatty acid oxidation may regulate the amount of energy available for protein synthesis in osteoblasts.A number of factors are required for fatty acid oxidation. For example, carnitine is the requisite carrier for the transport of long-chain fatty acids across the inner mitochondrial membrane into...

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L-carnitine affects osteoblast differentiation in NIH3T3 fibroblasts by the IGF-1/PI3K/Akt signalling pathway

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