title: Enterococcus faecalis attenuates the differentiation of macrophages into osteoclasts.
abstract: BACKGROUND
  Enterococcus faecalis is closely associated with refractory apical periodontitis, manifesting periapical lesions and alveolar bone loss. Macrophages playing an important role in the induction of inflammation can differentiate into bone-resorbing osteoclasts. In the present study, we investigated the effect of E. faecalis on the differentiation and function of macrophages as osteoclast precursors.
  
  
  METHODS
  Bone marrow-derived macrophages (BMMs) were differentiated into osteoclasts with macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B ligand in the presence or absence of heat-killed E. faecalis (HKEF). Tartrate-resistant acid phosphatase-positive multinucleated giant cells were analyzed to determine osteoclast differentiation. Western blotting was performed to examine the expression of c-Fos and NFATc1 transcription factors. Phagocytic capacity was analyzed by measuring uptake of carboxyfluorescein succinimidyl ester-labeled E. faecalis. Secretion of tumor necrosis factor-α, interleukin-6, keratinocyte-derived chemokine, and monocyte chemotactic protein-1 was determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Differentiation of BMMs into osteoclasts was attenuated in the presence of HKEF, and expression of c-Fos and NFATc1 was inhibited. HKEF exposure also prevented a reduction in the phagocytic capacity of BMMs after differentiation into osteoclasts. Concomitantly, HKEF induced the expression of chemokines monocyte chemotactic protein-1 and keratinocyte-derived chemokine and proinflammatory cytokines tumor necrosis factor-α and interleukin-6.
  
  
  CONCLUSIONS
  E. faecalis attenuated macrophages from differentiating into osteoclasts, allowing them to keep their ability to phagocytose and kill pathogens and to induce proinflammatory cytokine and chemokine secretion.
authors: Department of Oral Microbiology and Immunology, DRI and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors: Ok-Jin
authors: OJ
authors: Park
authors: Department of Oral Microbiology and Immunology, DRI and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors: Jihyun
authors: J
authors: Yang
authors: Department of Oral Microbiology and Immunology, DRI and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors: Jiseon
authors: J
authors: Kim
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Cheol-Heui
authors: CH
authors: Yun
authors: Department of Oral Microbiology and Immunology, DRI and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea. Electronic address: shhan-mi@snu.ac.kr.
authors: Seung Hyun
authors: SH
authors: Han
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D013293:Enterococcus faecalis; D008264:Macrophages / Q000502:physiology*; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000382:microbiology*; D010485:Periapical Periodontitis / Q000382:microbiology / Q000503:physiopathology; D010587:Phagocytosis
chemical_list: D018925:Chemokines; D016207:Cytokines
keywords: Chemokines; Enterococcus faecalis; cytokines; macrophages; osteoclast differentiation; phagocytosis