WNT4
Protein Wnt-4 precursor [UNQ426/PRO864]
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WNT signaling pathways play important roles in the behavior of human bone marrow stromal cells. Although WNT expression has been examined in human bone marrow stromal cells (hMSCs) with limited numbers of subjects or from commercial sources, there are conflicting results on WNT gene expression in hMSCs. Furthermore, the effects of age and gender on WNT expression in hMSCs are largely unknown. In this study, we evaluated RNA expression of all the WNT genes in hMSCs from 19 subjects, 12 women and 7 men, aged from 36 to 85 years. Analysis of WNT gene expression in young and old groups indicated that WNT7B and 14 were expressed significantly higher in the young group. WNT2 and WNT13 showed a trend of higher expression in young group. WNT7B, 13, and 14 were inversely correlated with age. Further analysis for gender-specific difference indicated that WNT16 was expressed significantly higher in men than in women. WNT11 showed a trend of higher expression in hMSCs from women. For the hMSCs from women, WNT13 was inversely correlated with age and WNT4 was positively correlated with age. For the hMSCs from men, WNT7B and WNT14 were inversely correlated with age. These data indicated that most of the age-related WNT genes belong to the canonical WNT signaling pathway. Further, there are gender-specific differences in the expression of WNT4, 7B, 13, 14, and 16 in hMSCs. Age and gender account for many of the sample-to-sample variations in WNT gene expression in human marrow stromal cells.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Bone Marrow Cells
- Cells, Cultured
- Female
- Gene Expression Regulation
- Humans
- Male
- Middle Aged
- Sex Characteristics
- Stromal Cells
- Wnt Proteins
Disorders of human sex determination result in malformations of the external and internal genitalia. These malformations may vary from sexual ambiguity to complete sex reversal (XY female, XX male). Most of the knowledge of the molecular mechanisms involved in the mammalian sex determination pathway has been derived from the genetic analysis of intersex patients. Clinical management of these conditions critically depends on a precise understanding of their pathophysiology. Until recently, only transcription factors such as SRY, SOX9, DAX1, WT1 and SF1 were known to be responsible for abnormal gonadal development and sexual ambiguity. Gonadal dysgenesis may be isolated, as in the case of SRY mutations, or associated with abnormal development of other organs, such as bone or adrenals, consistent with the spatial expression profile of the disrupted genes (SOX9 or SF1). WNT4 is a new sex-determining signalling molecule. Deletions of Wnt4 were shown to be responsible for the masculinization of XX mouse pups while its duplication and overexpression in humans leads to XY sex reversal. Similarly, duplications of loci containing DAX1 or SOX9 have also been shown to cause sex reversal. These results support the emerging concept that mammalian sex determination is dosage sensitive at multiple steps of its pathway.
MeSH Terms
- Aging
- Disorders of Sex Development
- Embryonic and Fetal Development
- Female
- Humans
- Male
- Ovary
- Sex Determination Processes
- Testis
- X Chromosome
- Y Chromosome