Altered Levels of mRNAs for Calcium-Binding/Associated Proteins, Annexin A1, S100A4, and TMEM64, in Peripheral Blood Mononuclear Cells Are Associated with Osteoporosis

Abstract

Background. Osteoporosis is the most common metabolic bone disease in the world. Since osteoporosis is clinically symptomless until the first fracture occurs, early diagnosis is critical. Calcium, along with calcium-binding and calcium-associated proteins, plays an important role in homeostasis, maintaining healthy bone metabolism. This study is aimed at investigating the level of calcium-binding/associated proteins, annexin A1, S100A4, and TMEM64, in peripheral blood mononuclear cells associated with osteoporosis and its clinical significance. Methods. The levels of mRNAs of annexin A1, S100A4, and TMEM64 in human peripheral blood mononuclear cells were evaluated among 48 osteopenia and 23 osteoporosis patients compared to 17 nonosteoporotic controls. Total RNAs were isolated from clinical samples, and quantitation of mRNA levels was performed using real-time quantitative PCR. Results. The levels of mRNAs for calcium-binding proteins, annexin A1 and S100A4, and calcium-associated protein, TMEM64, in human peripheral blood mononuclear cells were significantly reduced in osteopenia and osteoporosis patients compared with nonosteoporotic controls (one-way ANOVA, P<0.0001, P=0.039, and P=0.0195, respectively). Annexin A1 and TMEM64 mRNAs were also significantly reduced in female osteoporosis patients over the age of 50 years compared to nonosteoporotic controls (one-way ANOVA, P=0.004 and P=0.0037, respectively). ROC analysis showed that the reduction in the level of mRNA for annexin A1, S100A4, or TMEM64 in the patients’ peripheral blood mononuclear cells has a good diagnostic value for osteoporosis. Conclusions. The results show for the first time that calcium-binding/associated proteins, annexin A1 and TMEM64, could be future diagnostic biomarkers for osteoporosis.