title: In situ expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts of rat periodontal tissue.
abstract: OBJECTIVE
  This study examined the in situ expression of receptor activator of nuclear factor-kappaB ligand (RANKL), receptor activator of nuclear factor-kappaB (RANK), osteoprotegerin, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in the osteoclasts of rat periodontal tissue.
  
  
  BACKGROUND
  In periodontal disease, osteoclasts cause resorption of the alveolar bone. The function of osteoclasts is regulated by interaction with periodontal ligament cells (PDLs). Furthermore, various kinds of molecules such as RANKL, RANK, osteoprotegerin, IL-1beta and TNFalpha are known to be related to the osteoclasts differentiation and function. It is therefore important to observe the expression of RANKL, RANK, osteoprotegerin and cytokines in osteoclasts and PDLs.
  
  
  METHODS
  Four-week-old Wistar rats were used. Tooth movement was performed by the Waldo method, and the pathological bone resorption was induced. The demineralized maxillae and mandiblae were embedded with paraffin. In situ hybridization was performed to detect RANKL, RANK, osteoprotegerin, IL-1beta, and TNFalpha mRNAs in osteoclasts and other cells using the specific RNA probes, respectively.
  
  
  RESULTS
  Both RANKL and RANK were concomitantly expressed in some osteoclasts. RANKL was also positive in osteoblasts and PDLs. No IL-1beta- and TNFalpha-positive osteoclast was noted. The positive signals of osteoprotegerin were detected in almost all osteoblasts, PDLs and odontoblasts. No osteoprotegerin-positive osteoclasts were observed. The number and the distribution pattern of RANKL- and RANK-expressing osteoclasts changed when orthodontic excessive force was applied to periodontal tissue. In addition, IL-1beta and TNFalpha were shown to be expressed in osteoclasts under pathological status.
  
  
  CONCLUSIONS
  These findings suggest that an autocrine mechanism of RANKL-RANK exists in osteoclast, which is heightened in the pathological conditions. Furthermore, the autocrine mechanism of IL-1beta and TNFalpha is also provided in osteoclast under pathological condition. These autocrine mechanisms therefore seem to regulate the osteoclast function in both physiological and pathological conditions.
authors.affiliation: Department of Operative Dentistry and Endodontology, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ogasawara
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimine
authors.forename: T
authors.initials: T
authors.lastname: Kiyoshima
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.forename: A
authors.initials: A
authors.lastname: Akamine
authors.forename: H
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis*; D002452:Cell Count; D003583:Cytokinins / Q000032:analysis*; D006023:Glycoproteins / Q000032:analysis*; D007375:Interleukin-1 / Q000032:analysis; D008024:Ligands; D008562:Membrane Glycoproteins / Q000032:analysis*; D016328:NF-kappa B / Q000032:analysis*; D009804:Odontoblasts / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin; D010513:Periodontal Ligament / Q000378:metabolism / Q000473:pathology; D010519:Periodontium / Q000378:metabolism* / Q000473:pathology; D053245:RANK Ligand; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D014087:Tooth Movement Techniques; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D002352:Carrier Proteins; D003583:Cytokinins; D006023:Glycoproteins; D007375:Interleukin-1; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506032:Tnfrsf11b protein, rat; D014409:Tumor Necrosis Factor-alpha