Pre-clinical Analysis of Effects of Lamin A Overexpression on Mesenchymal Stem Cell Differentiation into Myocytes

Summary Falls and fractures are highly prevalent in the elderly. Around 20,000 hip fracture cases are reported in Australia every year, and nearly 25% of patients who sustain a hip fracture die within a year. Since a large number of fractures occur due to a fall, decrease in muscle size and strength with age (sarcopenia) seems to relate directly with the incidence of fall-related fractures.

Project Details

Both muscle cells (myocytes) and bone forming cells (osteoblasts) arise from the same precursor (mesenchymal stem cell; MSC), which makes this link biologically significant. MSCs are known to have an altered protein expression profile with age. Lamin A is a nuclear lamina protein associated with translocation of key translational factors affecting the bone formation pathways in MSCs. Lamin A expression is known to decrease with age in MSCs. This leads to the possibility of its role in muscle ageing too. We hypothesize that overexpression of Lamin Ain MSCs could reverse age-associated decrease in muscle cells.

We will use both in vitro and in vivo approaches in appropriate models to meet our goals. Students will be involved in in vitro studies involving MSC over-expression of Lamin A, differentiation of transformed MSCs into myocytes/osteoblasts/adipocytes, as well as in vivo tracking of injected MSCs in mice; bone histomorphometry and microCT analysis of mice/rat bones.