Effect of Vitamin C on pre-osteoblast gene expression.
Ascorbic acid (AA), also known as Vitamin C, is a cofactor required for the function of several hydroxylases. It is not synthesised in humans and has to be provided by diet. Its absence is responsible for scurvy, a condition related to the defective synthesis of collagen by the reduced function of prolylhydroxylase. AA is also a risk factor for periodontal disease. Recently, it has been shown that AA induces embryonic stem cells to differentiate into osteoblasts. The mechanism by which AA sustains pre-osteoblast proliferation and commitment is mediated through the synthesis of collagen type I, interaction with alpha2- and beta1-integrin, activation of the mitogen-activated protein kinase pathway, and phosphorylation of osteoblast-specific transcription factors. However, the multifunctional role of AA is not fully elucidated. MC3T3-E1 mouse calvaria-derived cell line is a well-defined in vitro model of pre-osteoblast differentiation, and AA is essential for the proliferation and differentiation of MC3T3-E1. By using DNA micro-arrays containing 15,000 genes, we identified several genes in MC3T3-E1 cultured with AA for 24h whose expression was significantly up or downregulated. The differentially expressed genes covered a broad range of functional activities: (1) cell growth; (2) metabolism; (3) morphogenesis; (4) cell death; (5) cell communication. The data reported are, to our knowledge, the first genetic portrait of early stage stimulation of pre-osteoblasts by AA, and may be relevant to better understand the molecular mechanism of pre-osteoblast proliferation and commitment. Elucidation of the molecular mechanism has important clinical implications because it may facilitate the correct use of AA to accelerate bone regeneration.
Carinci
Francesco
F
University of Ferrara, Italy.
Pezzetti
Furio
F
Spina
Anna Maria
AM
Palmieri
Annalisa
A
Laino
Gregorio
G
De Rosa
Alfredo
A
Farina
Ernesto
E
Illiano
Fausto
F
Stabellini
Giordano
G
Perrotti
Vittoria
V
Piattelli
Adriano
A
D016475:3T3 Cells; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D001205:Ascorbic Acid