Abstract
BackgroundSkeletal development and its cellular function are regulated by various transcription factors. The T-box (Tbx) family of transcription factors have critical roles in cellular differentiation as well as heart and limbs organogenesis. These factors possess activator and/or repressor domains to modify the expression of target genes. Despite the obvious effects of Tbx20 on heart development, its impact on bone development is still unknown.MethodsTo investigate the consequence by forced Tbx20 expression in the osteogenic differentiation of human mesenchymal stem cells derived from adipose tissue (Ad-MSCs), these cells were transduced with a bicistronic lentiviral vector encoding Tbx20 and an enhanced green fluorescent protein.ResultsTbx20 gene delivery system suppressed the osteogenic differentiation of Ad-MSCs, as indicated by reduction in alkaline phosphatase activity and Alizarin Red S staining. Consistently, reverse transcription-polymerase chain reaction analyses showed that Tbx20 gain-of-function reduced the expression levels of osteoblast marker genes in osteo-inductive Ad-MSCs cultures. Accordingly, Tbx20 negatively affected osteogenesis through modulating expression of key factors involved in this process.ConclusionThe present study suggests that Tbx20 could inhibit osteogenic differentiation in adipose-derived human mesenchymal stem cells.
Highlights
Bone is a dynamic tissue undergoing continuous remodeling, which is coordinately regulated by osteoblasts and osteoclasts [1]
The transcriptional regulatory networks involved in bone formation are rather well-defined, the discovery of new transcription factors involved in osteogenesis could further advance our understanding of normal and pathological bone development and homeostasis [4]
Identification of human Ad‐MSCs The mesenchymal stem cells isolated from human adipose tissue had a spindle-shaped fibroblastic appearance and could form single-cell
Summary
Bone is a dynamic tissue undergoing continuous remodeling, which is coordinately regulated by osteoblasts and osteoclasts [1]. The T-box (Tbx) family of transcription factors has widespread roles in development and response pathways [5, 6]. Based on the amino acid sequence of the T-box domain, Tbx family members are divided into five subfamilies: T, Tbx, Tbx, Tbx, and Tbr1 [8]. Skeletal development and its cellular function are regulated by various transcription factors. The T-box (Tbx) family of transcription factors have critical roles in cellular differentiation as well as heart and limbs organogen‐ esis. These factors possess activator and/or repressor domains to modify the expression of target genes. Despite the obvious effects of Tbx on heart development, its impact on bone development is still unknown
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