MicroRNA-338-3p regulates age-associated osteoporosis via targeting PCSK5

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.

Automated summary

Bone loss is highly associated with aging, and novel therapeutic strategies are urgently needed for age-associated osteoporosis. This study explored the association between PCSK5 and miR-338-3p in bone formation and loss processes. Results showed that miR-338-3p could suppress age-associated osteoporosis by regulating PCSK5 and downregulation of PCSK5 inhibited osteoblastic differentiation and osteogenesis.