Dysregulation of PIWI-interacting RNA-63049 (piRNA-63049) is associated with increased risk of post-menopausal osteoporosis in Chinese population via regulating the Wnt signaling pathway.

Abstract

This study investigates the association between PIWI-interacting RNA-63049 (piRNA-63049) and the risk of post-menopausal osteoporosis in a Chinese population. It explores piRNA-63049's role in modulating the Wnt signaling pathway, which is crucial for bone health, particularly in the context of estrogen deficiency-induced osteoporosis. We enrolled 216 participants divided into three groups: healthy control participants as the osteoporosis(-)fracture(-) group, osteoporosis patients without fractures as the osteoporosis(+)fracture(-) group, and osteoporosis patients with fractures as the osteoporosis(+)fracture(+) group. T-scores at both spine and hip were compared. The expression of piRNA-63049 and its impact on the Wnt/β-catenin signaling pathway were examined using polymerase chain reaction analysis and luciferase assays. Compared with other candidate piRNAs, piRNA-63049 exhibited significantly higher expression levels in patients with osteoporosis, while being highest in osteoporosis patients with fractures. T-scores of the osteoporosis(+)fracture(+) were also the lowest among all groups, which indicated worse bone health compared with the osteoporosis(+)fracture(-) group. Luciferase assays confirmed the molecular interactions between piRNA-63049 and the Wnt2b mRNA and β-catenin mRNA, both being crucial components of the Wnt signaling pathway. Overexpression of piRNA-63049 resulted in the downregulation of several key genes involved in bone metabolism, further elucidating its critical role in osteogenesis and bone health. Moreover, key genes of bone metabolism including LRP5, LRP6, OCN, OPN, and ALP were also regulated by the overexpression of piRNA-63049. Our study suggested that the dysregulation of piRNA-63049 is associated with the increased risk of post-menopausal osteoporosis and fractures in the Chinese population by modulating the Wnt/β-catenin signaling pathway. Key messages What is already known on this topic: Post-menopausal osteoporosis was recognized for its significant bone loss and increased fracture risk, largely due to estrogen deficiency disrupting bone remodeling. The Wnt signaling pathway was identified as a key regulator in bone metabolism, with its dysregulation linked to osteoporosis. However, the specific role of piRNA-63049 was not well understood, which requested further research into its regulatory functions and its connection to osteoporosis in the Chinese population. What this study adds: This study reveals that piRNA-63049 is significantly upregulated in post-menopausal osteoporosis patients, particularly in those with fractures, and demonstrates a direct molecular interaction between piRNA-63049 and the Wnt/β-catenin signaling pathway. How this study might affect research, practice, or policy: The study's findings have implications for developing targeted therapies for osteoporosis, as piRNA-63049's dysregulation may contribute to the pathogenesis of osteoporosis by negatively affecting bone metabolism genes. This could lead to new treatment strategies and improved clinical practices for managing post-menopausal osteoporosis.