The underlying mechanisms of the association of bone health with depression - an experimental study.

Background: Depression constitutes a risk factor for osteoporosis, but underlying molecular and cellular mechanisms are not fully understood. MiRNAs influence gene expression and are carried by extracellular vesicles (EV), affecting cell-cell communication.

Aims: (1) Identify the difference in miRNA expression between depressed patients and healthy controls; (2) Analyze associations of these miRNAs with bone turnover markers; (3) Analyze target genes of differentially regulated miRNAs and predict associated pathways regarding depression and bone metabolism.

Methods And Results: Blood samples from depressed patients (n = 11) were obtained from a previous study and healthy controls (n = 9) were recruited. Sociodemographic, depression diagnosis and depressive symptom (BDI-II) data were collected through questionnaires. Blood plasma was collected from each participant and real-time-quantitative PCR was performed on isolated plasma EVs; differences in miRNA expression between groups were analyzed using qbase+. Regression models assessed the associations of differentially regulated miRNAs with bone turnover markers procollagen-1 N-terminal-peptide, osteocalcin, and crosslaps; enriched pathways and miRNA target gene networks were analyzed. 19 miRNAs were differentially expressed between groups (p < 0.05). MiR-26b-5p and miR-106a-5p showed an association with procollagen-1 N-terminal-peptide; miR-330-5p and miR-377-3p were associated with osteocalcin, and miR-26b-5p, miR-34c-3p and miR-145 with crosslaps. Pathway analysis including the differentially expressed miRNAs predicted enriched pathways, including the FoxO signaling and p53 signaling pathway. Seven target genes were identified.

Conclusions: MiRNAs (e.g. miR-26b-5p, miR-377-3p), genes (TNRC6B, HSPA8), and pathways (FoxO- and Hippo-signaling pathway) are identified which could be mediators between the influence of depression on bone health and could possibly serve as biomarkers in the treatment of bone diseases among people with mental disorders.