title: Hyperocclusion up-regulates CCL3 expression in CCL2- and CCR2-deficient mice.
abstract: Excessive mechanical stress (MS) during hyperocclusion is known to result in disappearance of the alveolar hard line, enlargement of the periodontal ligament (PDL) space, and destruction of alveolar bone, leading to occlusal traumatism. We have recently reported that MS induces predominantly C-C chemokine ligand (CCL) 2 expression in PDL tissues, leading, via C-C chemokine receptor (CCR) 2, to MS-dependent osteoclastogenesis in alveolar bone. Thus, we hypothesize that ablation of the CCL2/CCR2 signaling pathway should suppress MS-induced osteoclastogenesis-associated chemokines and alleviate occlusal traumatism. We examined the effect of MS on chemokine expression and osteoclastogenesis using in vivo and in vitro hyperocclusion models with CCL2-deficient (CCL2((-/-))) and CCR2-deficient (CCR2((-/-))) mice. Compared with that in wild-type mice, expression of CCL3 in PDL cells and TRAP-positive cells in alveolar bone from CCL2((-/-)) and CCR2((-/-)) mice was up-regulated, even in the absence of MS. Furthermore, the expression of CCL3 and TRAP-positive cells was significantly increased after both 4 and 7 days of hyperocclusal MS loading in CCL2((-/-)) and CCR2((-/-)) mice. Hyperocclusion induced compensatory CCL3 expression and promoted osteoclastogenesis to counterbalance deficient CCL2/CCR2 signaling, suggesting that co-expression of CCL3 with CCL2 may precipitate synergistic, MS-dependent alveolar bone destruction during occlusal traumatism.
  
  
  BACKGROUND
  MS, mechanical stress; PDL, periodontal ligament; CCL2, CC chemokine ligand 2 (MCP-1; monocyte chemoattractant protein-1); CCR2, CC chemokine receptor 2; CCL3, CC chemokine ligand 3 (MIP-1α); CCL5, CC chemokine ligand 5 (RANTES).
authors.affiliation: Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsutsumi
authors.forename: H
authors.initials: H
authors.lastname: Kajiya
authors.forename: K T
authors.initials: KT
authors.lastname: Goto
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Okabe
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D016301:Alveolar Bone Loss / Q000276:immunology / Q000473:pathology; D000539:Alveolar Process / Q000276:immunology / Q000473:pathology; D000818:Animals; D001696:Biomechanical Phenomena; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000235:genetics*; D054405:Chemokine CCL3 / Q000032:analysis*; D018946:Chemokine CCL5 / Q000032:analysis; D003769:Dental Occlusion, Traumatic / Q000276:immunology / Q000473:pathology; D007527:Isoenzymes / Q000032:analysis; D008310:Malocclusion / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology; D010513:Periodontal Ligament / Q000276:immunology; D054389:Receptors, CCR1 / Q000032:analysis; D054390:Receptors, CCR2 / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013314:Stress, Mechanical; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; C515301:Ccr1 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D007527:Isoenzymes; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase