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Journal of molecular histology
Feb 13, 2025;56 (2): 87.

The Sirt1/FOXO signal pathway involves in regulating osteomyelitis progression via modulating mitochondrial dysfunctions and osteogenic differentiation.

Runyao Zhang, Nannan Kou, Feifei Liu, Huan Tong, Shaobo Li, Lirong Ren
Author Information
  1. Runyao Zhang: Department of Orthopedics, Guiqian International Hospital, No. 1 Dongfeng Avenue, Wudang District, Guiyang City, Guizhou Province, People's Republic of China.
  2. Nannan Kou: Department of Traumatology, The Second Affiliated Hospital of Kunming Medical University, No. 374, Dianmian Avenue. Wuhua District, Kunming City, Yunnan Province, People's Republic of China.
  3. Feifei Liu: Department of Spine Surgery, The First Affiliated Hospital of Dali University, No. 32, Jiashibo Avenue, Dali, Yunnan Province, People's Republic of China.
  4. Huan Tong: Department of Spine Surgery, The First Affiliated Hospital of Dali University, No. 32, Jiashibo Avenue, Dali, Yunnan Province, People's Republic of China.
  5. Shaobo Li: Department of Spine Surgery, The First Affiliated Hospital of Dali University, No. 32, Jiashibo Avenue, Dali, Yunnan Province, People's Republic of China.
  6. Lirong Ren: Department of Spine Surgery, The First Affiliated Hospital of Dali University, No. 32, Jiashibo Avenue, Dali, Yunnan Province, People's Republic of China. rlr306045105@163.com.
PMID: 39939446 DOI: 10.1007/s10735-025-10370-1

Abstract

The Sirtuin-1 (Sirt1) gene has been reported to be closely associated with the progression of multiple diseases, but its role in regulating osteomyelitis (OM) pathogenesis has not been explored. The murine long bone-derived osteocyte-like MLO-Y4 cells and osteoblast-like MC3T3-E1 cells were exposed to Staphylococcal protein A (SpA) treatment to establish the in vitro OM models. The expression levels of Osteoblast-specific genes (OCN, OPN and RUNX2), osteoclastic genes (CTSK, MMP9 and ACP5) and the FOXO pathway-related proteins (FOXO1, p-FOXO1, FOXO3 and p-FOXO3) were detected by performing Real-Time qPCR and Western Blot analysis. Osteoblastic differentiation of the cells were evaluated by using the alizarin red S staining assay and TRAP staining assay, and membrane potential and superoxide production were measured to evaluate the mitochondrial functions of the cells. SpA treatment significantly suppressed osteogenic differentiation and induced mitochondrial dysfunction in MLO-Y4 and MC3T3-E1 cells, and promoting osteoclastogenesis in RAW264.7 cells, suggesting that the in vitro OM models were successfully established. Of note, SpA decreased the expression levels of Sirt1 in the OM cells, and SpA-induced detrimental effects on the OM cells were all reversed by overexpressing Sirt1. Mechanistically, Sirt1-overexpression increased the levels of phosphorylated FOXO-related proteins (p-FOXO1 and p-FOXO3) to activate the FOXO signal pathway and ameliorated OM progression in SpA-treated cells. Collectively, it was revealed in the present study that overexpression of Sirt1 activated the FOXO signal pathway to ameliorate SpA-induced detrimental effects in the OM cells, and Sirt1 could be potentially used as therapeutic agent for OM in clinic.

Keywords

FOXO Mitochondrial dysfunction Osteomyelitis Sirt1 SpA

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Grants

  1. 202101AO070314/the special basic cooperative research programs of Yunnan provincial undergraduate universities
  2. 82460432/the Regional Science Foundation Project of the National Natural Science Foundation of China

MeSH Term

Sirtuin 1
Animals
Osteogenesis
Mice
Signal Transduction
Cell Differentiation
Mitochondria
Osteomyelitis
Disease Progression
RAW 264.7 Cells
Osteoblasts
Cell Line
Forkhead Transcription Factors
Forkhead Box Protein O1

Chemicals

Sirtuin 1
Sirt1 protein, mouse
Forkhead Transcription Factors
Forkhead Box Protein O1
Journal Article

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