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.

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

“…Signaling pathways include immune system [109], signal transduction [110], extracellular matrix organization [111], adaptive immune system [112], neutrophil degranulation [113], innate immune system [114], metabolism [115], diseases of metabolism [116] and Hemostasis [117] were responsible for advancement of COPD. MPO (myeloperoxidase) [190], CTSD (cathepsin D) [1389], KLF10 [1390], FRZB (frizzled related protein) [1391], DUSP1 [1392], IL1B [1393], CCL11 [1394], LMNA (lamin A/C) [1395], WIF1 [1396], IL1RN [1397], IFNG (interferon gamma) [1398], CX3CL1 [1399], BMP2 [1400], CDKN1A [1401], BMP4 [1402], ICAM1 [1403], CD34 [1404], IL33 [1405], FASLG (Fas ligand) [1406], KDM6B [1407], TNF (tumor necrosis factor) [1408], GDF15 [1409], IL2 [1410], INPP4B [1411], FABP4 [1412], CYP2C19 [1413], CXCR4 [1414], DKK2 [1415], PLCB4 [1416], ANXA1 [1417], DUSP6 [1418], CORIN (corin, serine peptidase) [1419], F8 [1420], DDIT4 [1421], IL1R2 [1422], S100A4…”

Identification of hub genes associated with osteoporosis development by comprehensive bioinformatics analysis

“…According to the World Health Organization (WHO) reports, OP has become one of the most common diseases in the world, with 30%-50% of women worldwide suffering from fracture due to OP in their lifetime (Rachner et al, 2011). Since OP doesn't have any obvious clinical symptoms before the occurrence of the first fracture, early diagnosis is key to timely intervention and to alleviating the pain of patients (Dera et al, 2019;Yong and Logan, 2021). Compared to previous studies (Chen et al, 2021), our studies not only screened genes related to OP occurrence and development in the GSE database, but also verified the correlation and differential expressions between core genes and the data set.…”

Machine learning analysis of gene expression profile reveals a novel diagnostic signature for osteoporosis

“…According to the World Health Organization (WHO), OP has become one of the most common diseases, and 30–50% of all women worldwide will undergo fractures because of OP throughout their lives [ 23 ]. On the other hand, since OP is clinically symptomless until the first fracture occurs, early diagnosis is more critical and contributes to timely intervene OP to relieve the patient’s pain [ 24 ]. In this study, we identified 176 genes that might be related to the occurrence and development of OP through WGCNA analysis.…”