Expression of Senescence and Osteoporosis-Associated microRNAs in Human Bone and Their Correlations With Clinical Parameters of Osteoporotic Patients.

Abstract

Osteoporosis is an age-related disease associated with impaired bone remodeling and cellular senescence. MicroRNAs (miRNAs) play an important regulatory role in these processes. This study aimed to identify senescence-associated miRNAs in human osteoporotic bone tissue and to assess their relationship with clinical parameters. A total of 46 patients undergoing total hip arthroplasty were included in this single-center cross-sectional study, representing a relatively large and unique cohort of human bone tissue samples: 21 with osteoporotic proximal femur fracture and 25 with elective arthroplasty for osteoarthritis as controls. Total RNA was isolated from femoral neck biopsies, and the relative expression of 11 selected miRNAs was quantified by qRT-PCR and expressed using 2^-DeltaDeltaCt method. Data were analyzed using t-tests, correlation analysis, and generalized linear models (GLM). MiR-106a-5p was significantly upregulated in osteoporotic patients, whereas miR-34a-5p, miR-218-5p, and miR-155-5p were significantly downregulated. After adjustment for clinical variables, miR-106a-5p remained independently positively associated with osteoporosis, while miR-34a-5p and miR-218-5p showed independent negative associations. MiR-92a-3p and miR-181a-5p became significantly associated with osteoporosis only after adjustment. Network analysis linked the dysregulated miRNAs to genes involved in DNA damage response and cell-cycle control. Osteoporosis is associated with a specific senescence-related miRNA signature in human bone tissue. Integration of molecular and clinical data improved the interpretation of miRNA-disease associations and supports the potential of selected miRNAs as biomarkers of bone aging and osteoporosis. Key words Cellular senescence " Bone metabolism " Osteoporosis " Bone biopsies " miRNA.