Introduction
Trisomy 21 (T21) or Down syndrome (DS) is a common genetic anomaly caused by the triplication of chromosome 21. Individuals with DS face significant bone health challenges, an area not extensively studied. As the DS population ages, the prevalence of osteoporosis rises.
Early-onset osteoporosis (EOO), characterised by reduced bone density and altered bone structure, increases fracture risk. Recognized as a "silent epidemic," osteoporosis has substantial health and economic implications. There is an urgent need to understand the factors exacerbating bone issues in DS, given their increased fracture risk and reduced healing capacity, impacting their overall quality of life.
Aims
We aim to understand how T21 affects bone health, particularly osteoblast differentiation and function. EOO in DS is believed to stem from compromised osteoblastic activities, leading to decreased bone mass. The study will explore osteoblast efficiency, maturation, and function using hiPSCs from WT and individuals with T21, seeking insights into how T21 influences osteoblasts and EOO in DS. Findings may guide future specialized treatments.
Methods
This study examines hiPSCs as a new model to explore bone health in T21. We use cell lines from WT individuals and those with T21. Through in vitro cell culture experiments, we investigate osteoblastic differentiation via WST-1 and qPCR analysis, maturation with Alizarin Red staining, and functionality via immunofluorescence. We also plan to assess proliferation, senescence and apoptosis using Western Blot.
Expected outcomes
We hypothesise that osteoblast differentiation will be reduced as evidenced by a decrease osteoblast markers expression at both the mRNA and protein levels. We anticipate reduced osteoblast maturation, functionality, and cellular proliferation with an increase in osteoblast senescence and apoptosis.
Conclusion
By elucidating the cellular processes altered in the bone of T21 individuals, these findings will improve bone health management for individuals with DS, thus significantly enhancing their quality of life.