Osteoporosis is a major public health problem, especially in women. It is mainly characterized by low bone mineral density (BMD). Women have much lower BMD than men. Some BMD genes/genomic regions are sex-specific.
Menopause is associated with rapid bone loss.
Bone marrow mesenchymal ;stem cells (BMMSCs) and peripheral blood monocytes (PBMs), are precursors for osteoblasts (bone formation cells) and osteoclasts (bone resorption cells), respectively.
The GOAL of this project is to identify genes that are differentially expressed (at mRNA& levels) in BMMSCs and PBMs in females with low vs. high BMD and with menopausal status changes. Such genes are expected to be important for variation of female BMD and women health in general.
We are recruiting otherwise healthy females aged 50-55, stratified by discordant BMD values and menopausal status. Bone marrow aspiration
and phlebotomy will be performed on the recruited subjects to isolate BMMSCs; and PBMs. Total RNA will be extracted from the isolated cells. Using the total RNA extracted, microarray ;profiling experiments and analyses will be performed for gt;40,000 known human genes and ESTs to identify differentially expressed genes/ESTs in low vs. high BMD subjects, which will be further verified with real-time RT-PCR.
As preliminary studies for this project, we have published several papers on microarray profiling of PBMs& in high vs. low BMD subjects (J.Biol& Chem. 2005 12;280(32):29011-6; J Bone Miner Res. 2010 25(2):339-55; Bone. 2009 44(5):1010-4). These studies have identified several interesting genes/proteins important to osteoporosis.