RRP12 knockdown inhibited inflammation and p53/NF-κB pathway and alleviated heterotopic ossification in mice
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Authors
Heterotopic ossification (HO) is a pathological process, featured by the aberrant mature bone tissue in soft tissues outside the normal skeletal system, commonly occurring following trauma or major joint surgery. Ribosomal RNA Processing 12 Homolog (RRP12) has been confirmed to display multiple roles in ribosome synthesis, DNA damage, cell cycle and cell differentiation processes. However, the regulatory influences of RRP12 in HO progression keep vague and require further investigation. In this project, it was illustrated that RRP12 expression was markedly up-regulated in HO mice. Inhibition of RRP12 retarded the progression of HO in mice. Furthermore, RRP12 knockdown alleviated inflammation. Besides, it was revealed that suppression of RRP12 inactivated the p53/NF-κB pathway. Lastly, in bone marrow mesenchymal stem cells (BMSCs), it was verified that knockdown of RRP12 suppressed osteogenic differentiation of BMSCs. In conclusion, RRP12 knockdown inhibited inflammation and p53/NF-κB pathway and alleviated HO in mice. This study not only expands the current understanding of the molecular underpinnings of HO but also identifies RRP12 as a potential actionable target for therapeutic intervention. Nonetheless, further investigations are warranted to delineate the upstream regulators of RRP12 and to evaluate its translational feasibility in clinical settings.
Ethics Approval
The animal experiments were approved by the Ethics Committee of Lu'an People’s HospitalCRediT authorship contribution
Yuchen Hu, conceptualization, methodology, investigation, writing – original draft, writing – review & editing. Zihao Zeng, conceptualization, methodology, investigation, writing – original draft, writing – review & editing. Wen Jin, conceptualization, methodology, investigation, writing – original draft, writing – review & editing. Chenggang Wang, supervision, data curation, formal analysis. Xiaofeng Liu, formal analysis. Yusheng Sun, validation. Qing Gao, validation.
Supporting Agencies
Science and Technology Project of Bengbu Medical UniversityData Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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