AUTHOR=Zheng Linlin , Sun Hui , Li Ning , Wang Lianqing , Li Tianchu , Zhai Qiaoli 
  
TITLE=RNA splicing in bone diseases: mechanisms, pathogenesis and therapeutics
  
JOURNAL=Acta Biochimica Polonica
  
VOLUME=Volume 72 - 2025
  
YEAR=2026
  
URL=https://www.frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2025.15819
  
DOI=10.3389/abp.2025.15819
  
ISSN=1734-154X
  
ABSTRACT=RNA splicing is a fundamental post-transcriptional mechanism that enables the generation of diverse mRNA isoforms from a single gene, thereby expanding proteomic complexity and regulating cell fate decisions. Emerging evidence highlights that dysregulated splicing contributes to the onset and progression of various bone-related diseases, including osteoporosis, osteoarthritis, and skeletal malignancies. In this review, we summarize current knowledge on the core mechanisms of pre-mRNA splicing, with emphasis on alternative splicing events that modulate bone cell differentiation, matrix formation, and tissue homeostasis. We further discuss how aberrant splicing impacts signaling pathways involved in bone metabolism and disease pathogenesis, and we explore the epigenetic and RNA-binding protein networks that fine-tune these processes. Finally, we examine the therapeutic potential of targeting splicing machinery or correcting mis-splicing events using small molecules, antisense oligonucleotides, and RNA-based approaches. This comprehensive overview provides mechanistic insights and highlights splicing regulation as a promising avenue for the diagnosis and treatment of skeletal disorders.