Abstract 35

Microarray study of bone marrow stromal cells from osteoporosis

Yin Xiao¹, Huihua Fu ², Yaw-Ching Yang³, Ross Crawford ¹, Jeffrey Hollinger ²

¹QUT, Brisbane, Australia; ²BTEC, CMU, Pittsburgh, USA; ³ WRI, Johnstown, USA

Ageing of the human skeleton is characterized by decreased bone formation and bone mass. These changes are more pronounced in patients with osteoporosis. We propose decreased bone formation as a consequence of ageing and osteoporosis may be explained by different genetic profiling of bone marrow stem cells, which results in decreasing of osteogenic differentiation.

To test this hypothesis, microarray experiments were designed to identify the genetic profile of bone marrow stromal cells from juvenile, geriatric, osteoporotic, and normal adult rats. Osteoporotic animal model was generated from ovariectomy. Bone marrow stem cells were isolated by flushing the femurs and subcultured by the first passage. Total RNA was extracted from the first passaged cells and further processed for the microarray study. The animal model was verified by examination of the animal's tibia and femur histology. Identified genes were further verified by quantitative PCR. There were 1025 genes detected with significant differences between normal and osteoporotic rats. There was more than 2-fold up-regulation in 194 genes and a 2-fold down-regulation in 108 genes in osteoporosis compared with normal rat. Lipoprotein lipase (Lpl), cellular retinoic acid binding protein 2, osteoglycin precursor, osteoclast inhibitory lectin, retinoic acid inducible protein 3, Neuropeptide Y (Npy) are the most relevant genes identified in regulating cell differentiation and osteogenesis, which were differently expressed in osteoporosis compared with normal rat. Therefore, difference in genetic profiling of bone marrow stem cells plays a potential role in osteogenesis in osteoporosis.

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