The role of human β‐defensin‐2 in bone

Osteomyelitis often causes functional impairment due to tissue destruction. This report demonstrates a novel previously unappreciated role of osteoblasts. Samples of osteomyelitic bone and bacterially challenged osteoblasts produce increased amounts of antimicrobial peptides in order to combat bacte...

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Bibliographic Details
Published in:Journal of anatomy 2008-12, Vol.213 (6), p.749-757
Main Authors: Varoga, D., Tohidnezhad, M., Paulsen, F., Wruck, C. J., Brandenburg, L., Mentlein, R., Lippross, S., Hassenpflug, J., Besch, L., Müller, M., Jürgens, C., Seekamp, A., Schmitt, L., Pufe, T.
Format: Article
Language:English
Subjects:
Aged
Animals
Anti-Infective Agents - metabolism
antimicrobial peptides
beta-Defensins - genetics
beta-Defensins - metabolism
bone
Bone and Bones - metabolism
Case-Control Studies
Cell Line
Dexamethasone - therapeutic use
Enzyme-Linked Immunosorbent Assay - methods
Gene Expression - drug effects
human beta defensin‐2
Humans
Immunohistochemistry
Immunosuppressive Agents - therapeutic use
innate immunity
Male
Methotrexate - therapeutic use
Mice
Mice, Inbred BALB C
Middle Aged
Models, Animal
Original
Osteoblasts - metabolism
Osteomyelitis - drug therapy
Osteomyelitis - metabolism
Reverse Transcriptase Polymerase Chain Reaction - methods
Staphylococcal Infections - metabolism
Staphylococcus aureus
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Summary:Osteomyelitis often causes functional impairment due to tissue destruction. This report demonstrates a novel previously unappreciated role of osteoblasts. Samples of osteomyelitic bone and bacterially challenged osteoblasts produce increased amounts of antimicrobial peptides in order to combat bacterial bone infection. An osteomyelitis mouse model confirmed the osseous induction of the murine homologue of human β‐defensin‐2, suggesting a central role in the prevention of bacterial bone infection. Antimicrobial peptides are effectors of the innate defence system and play a key role in host protection at cellular surfaces. Some of them are produced constitutively, whereas others are induced during infection. Human β‐defensins represent a major subclass of antimicrobial peptides and act as a first line of defence through their broad spectrum of potent antimicrobial activity. The aim of the present in‐vitro and in‐vivo investigations was to study the expression and regulation of human β‐defensin‐2 in the case of bacterial bone infection and to analyse the effects of immunosuppressive drugs on bone‐derived antimicrobial peptide expression. Samples of healthy human bone, osteomyelitic bone and cultured osteoblasts (hFOB cells) were assessed for the expression of human β‐defensin‐2. Regulation of human β‐defensin‐2 was studied in hFOB cells after exposure to bacterial supernatants, proinflammatory cytokines and immunosuppressive drugs (glucocorticoids and methotrexate) and was assayed by enzyme‐linked immunosorbent assay. An osteomyelitis mouse model was performed to demonstrate the regulation of the murine homologue of human β‐defensin‐2, named murine β‐defensin‐3, by real‐time reverse transcription‐polymerase chain reaction and immunohistochemistry. Healthy human bone and cultured osteoblasts are able to produce human β‐defensin‐2 under standard conditions. Samples of infected bone produce higher levels of endogenous antibiotics, such as human β‐defensin‐2, when compared with samples of healthy bone. A clear induction of human β‐defensin‐2 was observed after exposure of cultured osteoblasts to Gram‐positive bacteria or proinflammatory cytokines. Additional treatment with glucocorticoids or methotrexate prevented bacteria‐mediated antimicrobial peptide induction in cultured osteoblasts. The osteomyelitis mouse model demonstrated transcriptional upregulation of the murine homologue of human β‐defensin‐2, namely murine β‐defensin‐3, in bone after intraosseous cont
ISSN:0021-8782
1469-7580
DOI:10.1111/j.1469-7580.2008.00992.x