BoneKEy Reports | BoneKEy Watch
Gene expression differences in MSCs and their relevance to osteoporosis
DOI:10.1038/bonekey.2012.257
In an effort to discover more about the deficiencies in anabolic bone activity and regeneration that may underlie osteoporosis, this study used microarray analyses of multipotent mesenchymal stem cells (MSCs) from different population groups.
Firstly, MSCs from elderly (age 79–94 years) osteoporotic patients were compared with MSCs from age-matched controls who did not have osteoporosis. The MSCs from osteoporotic patients showed significantly increased mRNA expression of several osteoblastic genes, including RUNX2, LRP5 and COL1A1. Genes associated with bone formation were also more highly expressed, including those coding for WNT and BMP inhibitors.
In another series of analyses, MSCs from the two groups described above were also compared with MSCs from donors 30 years younger. This suggested that most of the gene expression changes that occur in elderly patients with osteoporosis arise due to effects that are independent of the aging process itself. The transcriptional changes that accompany the disease process are distinct and specific to the course of the osteoporosis.
Editor’s comment: The results obtained by comparing the gene expression profiles of MSCs from elderly and middle-aged osteoporotic donors provide interesting hypotheses on the potential mechanisms that underlie the decline in bone formation relevant to age and bone fragility. They also provide further evidence for a truly causal association between osteoporosis and some of the genes identified by GWAS.
Limitations of the study include the small number of samples compared initially and the lack of sample replication, which make it difficult to ascertain which genes are actually differentially expressed between osteoporotic and senescent MSCs
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