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Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3
- Source :
- Histochemistry and Cell Biology. 131:207-218
- Publication Year :
- 2008
- Publisher :
- Springer Science and Business Media LLC, 2008.
-
Abstract
- Gram-positive bacterial bone infections are an important cause of morbidity particularly in immunocompromised patients. Antimicrobial peptides (AP) are effectors of the innate immune system and directly kill microorganisms in the first hours after microbial infection. The aim of the present investigation was to study the expression and regulation of gram-positive specialized human beta-defensin-3 (HBD-3) in bone. Samples of healthy and osteomyelitic human bone were assessed for the expression of HBD-3. Using primary and immortalized osteoblasts (SAOS-2 cells), release and regulation of HBD-3 was evaluated after exposure to Staphylococcus aureus supernatant and/or corticosteroids using PCR, immunohistochemistry, Western blot and ELISA. To determine the role of toll-like-receptors-2 and -4 (TLR-2/-4), shRNA was used to downregulate TLRs. An osteomyelitis mouse model was created performed to investigate the release of murine beta-defensins using immunohistochemistry and RT-PCR. Cultured osteoblasts and human bone produce HBD-3 under standard conditions. The release increases within hours of bacterial supernatant exposure in cultured osteoblasts. This observation was not made in chronically infected bone samples. The shRNA-technology revealed the necessity of TLR-2 and -4 in HBD-3 induction in osteoblasts. Blocking protein synthesis with cycloheximide showed that the rapid release of HBD-3 is not dependent on a translational de novo synthesis and is not affected by glucocorticoids. The murine osteomyelitis model confirmed the in vivo release uptake of mouse beta-defensins-4 (MBD-4) in bone. This report shows the bacterial induction of HBD-3 via TLR-2 and -4 in osteoblasts and suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection. The rapid and effective induction of HBD-3 in osteoblasts incubated with conditioned media from bacteria is more likely a result of a rapid secretion of preformed HBD-3 by osteoblasts rather than a result of enhanced biosynthesis. The increased incidence of gram-positive bacterial bone infection in patients with regular intake of glucocorticoids does not seem to be caused by a deranged HBD-3 release in osteoblasts.
- Subjects :
- Staphylococcus aureus
beta-Defensins
Histology
Antimicrobial peptides
Cycloheximide
Biology
Bone and Bones
Microbiology
Bone Infection
Mice
chemistry.chemical_compound
Western blot
Adrenal Cortex Hormones
In vivo
medicine
Animals
Humans
Secretion
Molecular Biology
Osteoblasts
Innate immune system
medicine.diagnostic_test
Osteomyelitis
Cell Biology
Toll-Like Receptor 2
Toll-Like Receptor 4
Kinetics
Medical Laboratory Technology
Beta defensin
Gene Expression Regulation
chemistry
Subjects
Details
- ISSN :
- 1432119X and 09486143
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- Histochemistry and Cell Biology
- Accession number :
- edsair.doi.dedup.....4ffc3a2c6752e1db225ce301b1f7bd6c