RESUMO
UNLABELLED: 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. ABBREVIATIONS: 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).
Assuntos
Quimiocina CCL2/genética , Quimiocina CCL3/análise , Má Oclusão/imunologia , Receptores CCR2/genética , Fosfatase Ácida/análise , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/patologia , Processo Alveolar/imunologia , Processo Alveolar/patologia , Animais , Fenômenos Biomecânicos , Técnicas de Cultura de Células , Quimiocina CCL5/análise , Oclusão Dentária Traumática/imunologia , Oclusão Dentária Traumática/patologia , Isoenzimas/análise , Má Oclusão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoclastos/patologia , Osteoclastos/fisiologia , Ligamento Periodontal/imunologia , Receptores CCR1/análise , Transdução de Sinais/genética , Estresse Mecânico , Fosfatase Ácida Resistente a Tartarato , Fatores de Tempo , Regulação para Cima/genéticaRESUMO
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 hypothesized that MS induces expression of osteoclastogenesis-associated chemokines in PDL tissue, resulting in chemotaxis and osteoclastogenesis during occlusal traumatism. We examined the effect of MS on relationships between chemokine expression and osteoclastogenesis using in vivo and in vitro hyperocclusion models. In an in vitro model, intermittent stretching-induced MS was shown to up-regulate the expression of CC chemokine ligand (CCL)2, CCL3, and CCL5 in PDL cells. The expression levels of CCL2 in PDL tissues, its receptor CCR2 in pre-osteoclasts, and tartrate-resistant acid-phosphatase-positive cells in alveolar bone were significantly up-regulated 4-7 days after excessive MS during hyperocclusion in in vivo rodent models. Hyperocclusion predominantly induced CCL2 expression in PDL tissues and promoted chemotaxis and osteoclastogenesis, leading to MS-dependent alveolar bone destruction during occlusal traumatism.
