MicroRNA?338?3p regulates age?associated osteoporosis via targeting PCSK5.

ABSTRACT: Bone loss is a disease that is highly associated with aging. This deleterious health condition has become a public concern worldwide, and there is an urgent need to discover more novel therapeutic strategies for the development of age?associated osteoporosis. The present study aimed to explore the association between proprotein convertase subtilisin/kexin type 5 (PCSK5) and microRNA(miR)?338?3p in bone?formation and bone?loss processes. Western blotting assay and reverse transcription?quantitative PCR were employed to analyze PCSK5 and miR?338?3p expression levels in bone mesenchymal stem cells (BMSCs). Dual?luciferase reporter and RNA pull?down assays were used to determine the target. For osteoblastic differentiation verification, alkaline phosphatase activity, osteocalcin secretion detection, bone formation?related indicators (osterix, runt?related gene 2, osteopontin and bone sialoprotein), hematoxylin and eosin staining and Alizarin Red S staining were performed. The findings of the present study indicated that the expression level of PCSK5 was higher in BMSCs from young rat samples, whereas the expression level of miR?338?3p was higher in BMSCs from samples of old rats. Experimental results also revealed that unlike miR?338?3p, downregulation of PCSK5 inhibited osteoblastic differentiation and osteogenesis by inhibiting alkaline phosphatase, osteocalcin, osterix, runt?related transcription factor 2, osteopontin, bone sialoprotein and mineralized nodule formation. Overall, the results suggested that miR?338?3p could suppress age?associated osteoporosis by regulating PCSK5.

SUBMITTER: Tong J 

PROVIDER: S-EPMC7751475 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature