Association of TWIST1 gene polymorphisms with bone mineral density in postmenopausal women

Abstract

These results suggest that TWIST1 may be a useful genetic marker for osteoporosis and may have a role on bone metabolism in humans. Our results provide preliminary evidence supporting an association of TWIST1 with osteoporosis in postmenopausal women.

Pivotal role of Twist in skeletal biology and pathology

“…Up to now, no data are available on the role of Twist1 in age-related bone loss. However, recent data indicate that Twist1 gene polymorphisms are associated with altered bone mineral density in postmenopausal women (Hwang et al, 2010), which strongly suggests a role for Twist1 in the control of bone loss associated with aging. A possible functional role of Twist1 in the defective mesenchymal cell fate associated with age-related bone loss opens new areas of research, and may have important implications in developping therapeutic strategies targeting Twist1 for the treatment of skeletal disorders in which the mesenchymal cell pool is compromised.…”

“…The significant contribution of Twist1 in the process of osteoblast differentiation may have important implications in clinical situations where osteoblastogenesis is compromised. For example, recent genetic data indicate that Twist1 may have a role in bone loss in postmenopausal women (Hwang et al, 2010). This suggests that abnormal Twist1 expression or function in cells of the osteoblast lineage may be, in part, involved in age-related defective osteoblastogenesis.…”

TWIST1 and TSG6 are coordinately regulated and function as potency biomarkers in human MSCs

“…These results are consistent with observed interdonor differences in potency and suggest that genetic or epigenetic factors may contribute to such differences. Several genetic alterations including single-nucleotide polymorphisms have been identified at the TWIST1 locus that are associated with susceptibility to breast cancer ( 58 ), prognosis in gastric cancer ( 59 ), and osteoporosis ( 60 ). Fifth, while our studies focused on BM-MSCs, we show that these relationships extend to iPSC-MSCs, which were found to express significantly higher and lower TWIST1 and TSG6 levels, respectively, as compared to BM-MSCs, and exhibit weak anti-inflammatory activity in vivo when expanded in monolayers as predicted by the CLIP scale.…”

Screening and functional microarray analysis of differentially expressed genes related to osteoporosis

“…BMD is known to be highly heritable, and an increasing number of genes have been identified to have independent effects on BMD in osteoporosis, including pre-B-cell leukemia homeobox 1 (PBX1) (Cheung et al, 2009), apolipoprotein E (APOE) (Singh et al, 2010), Jagged1 (JAG1) (Kung et al, 2010), TWIST1 gene (Hwang et al, 2010), TN-FRSF11B (osteoprotegerin) (Vidal et al, 2011), and SOX6 (Yang et al, 2012). In addition, in osteoporotic women, femoral neck BMD shows associations with vitamin D receptor gene (VDR), and lumbar spine BMD with osteoprotegerin (OPG) and tumor necrosis factor superfamily member 11 (TNFSF11) (Mencej-Bedrač et al, 2009).…”