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B. Abortus Modulates Osteoblast Function Through the Induction of Autophagy.
- Source :
-
Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2018 Dec 04; Vol. 8, pp. 425. Date of Electronic Publication: 2018 Dec 04 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Osteoarticular brucellosis is the most common localization of human active disease. Osteoblasts are specialized mesenchymal-derived cells involved in bone formation and are considered as professional mineralizing cells. Autophagy has been involved in osteoblast metabolism. The present study demonstrates that Brucella abortus infection induces the activation of the autophagic pathway in osteoblast cells. Autophagy was revealed by upregulation of LC3II/LC3I ratio and Beclin-1 expression as well as inhibition of p62 expression in infected cells. Induction of autophagy was also corroborated by using the pharmacological inhibitors wortmannin, a PI 3-kinase inhibitor, and leupeptin plus E64 (inhibitors of lysosomal proteases). Autophagy induction create a microenvironment that modifies osteoblast metabolism by the inhibition of the deposition of organic and mineral matrix, the induction of matrix metalloproteinase (MMP)-2, osteopontin, and RANKL secretion leading to bone loss. Accordingly, autophagy is also involved in the down-modulation of the master transcription factor in bone formation osterix during B. abortus infection. Taking together our results indicate that B. abortus induces the activation of autophagy pathway in osteoblast cells and this activation is involved in the modulation of osteoblast function and bone formation.
- Subjects :
- Beclin-1 metabolism
Bone Matrix metabolism
Bone Matrix microbiology
Cell Differentiation
Cell Line
Collagen metabolism
Cytokines metabolism
Humans
Matrix Metalloproteinase 2 metabolism
Microtubule-Associated Proteins metabolism
Osteogenesis
Osteopontin
Phosphatidylinositol 3-Kinases
RANK Ligand metabolism
RNA-Binding Proteins metabolism
Autophagy
Brucella abortus pathogenicity
Brucellosis pathology
Osteoblasts metabolism
Osteoblasts microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 2235-2988
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Frontiers in cellular and infection microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 30564561
- Full Text :
- https://doi.org/10.3389/fcimb.2018.00425