SNORD31

Description

Age-related osteoporosis is characterized by impaired bone formation and chronic low-grade inflammation; however, the mechanisms coordinating bone marrow mesenchymal stem cell (BMSC) senescence and inflammaging remain incompletely understood. Here, we identified SNORD31, an evolutionarily conserved small nucleolar RNA, as a critical regulator of skeletal aging. SNORD31 expression was significantly reduced in aged bone tissues and senescent BMSCs across human and rodent datasets. Functional studies demonstrated that SNORD31 deficiency accelerated bone loss in young mice, whereas restoration of SNORD31 expression alleviated age-associated osteoporosis in aged mice. Mechanistically, SNORD31 exerted both intracellular and microenvironmental anti-aging effects. In BMSCs, SNORD31 directly interacted with MDM2 mRNA and enhanced its stability, thereby suppressing p53-dependent senescence signaling. In parallel, extracellular SNORD31 attenuated macrophage inflammatory activation through modulation of TLR4 signaling. Functionally, SNORD31 promoted BMSC proliferation and osteogenic differentiation while inhibiting adipogenesis and cellular senescence. Furthermore, SNORD31 expression was positively regulated by NRF2 but negatively regulated by p53, forming a feedback regulatory loop during skeletal aging. Collectively, these findings identify SNORD31 as a central regulator of bone aging and suggest that targeting snoRNA-mediated senescence and inflammaging may represent a potential therapeutic strategy for age-related osteoporosis.

Institutions

• Central South University

  Hunan, Changsha

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