Evidences of the cooperative role of the chemokines CCL3, CCL4 and CCL5 and its receptors CCR1+ and CCR5+ in RANKL+ cell migration throughout experimental periodontitis in mice

The Role of Chemokines and Cytokines in the Pathogenesis of Periodontal and Periapical Lesions: Current Concepts

“…However, the pro-inflammatory effect of IFN- demonstrated in vivo, leading to the upregulation of TNF- and IL-1 levels (and consequently RANKL) seems to overcome the direct anti-osteoclastogenic effect described in vitro (Gao et al, 2007. In addition, IFN- also stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation or through the chemoattraction of RANKL+ cells (Gao et al, 2007, Garlet et www.intechopen.com al., 2008, Repeke et al, 2010). This finding is supported by a recent study, which demonstrates that Th1 cells (characterized as CD3+CCR5+CXCR3+ cells) are an important source of RANKL throughout experimental periodontitis (Repeke et al, 2010).…”

“…In addition, IFN- also stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation or through the chemoattraction of RANKL+ cells (Gao et al, 2007, Garlet et www.intechopen.com al., 2008, Repeke et al, 2010). This finding is supported by a recent study, which demonstrates that Th1 cells (characterized as CD3+CCR5+CXCR3+ cells) are an important source of RANKL throughout experimental periodontitis (Repeke et al, 2010). An additional evidence of the adverse effect of Th1 response concerning periodontal tissue destruction indicates the role of IL-12 (the major Th1-inducing cytokine) mediating alveolar bone loss in mice after P. gingivalis challenge .…”

“…Accordingly, an increased amount of orthodontic tooth movement, correlated with increased alveolar bone resorption, was observed in the absence of CCR5 in mice (Andrade Jr. et al, 2009). Interestingly, an intermediate phenotype of PD development was observed after individual blockage of CCR1 and CCR5 (using genetically deficient mice strains) (Repeke et al, 2010). Thus, supported by findings that showed CCR1 expression in pre-osteoclasts and its increase expression in RANKL differentiated osteoclasts (Yu et al, 2004), it seems that the bone resorptive activity of CCL5 in PD and PL might be mediated by its engagement with CCR1, while it seems to be controlled by CCR5, although lack direct evidence to support this hypothesis.…”

“…The number of CCL3-positive cells increases in periodontal tissues with increasing severity of PD. On the other hand, the absence of CCL3 does not affect the development of experimental PD in mice, probably due to the presence of homologous chemokines CCL4 and CCL5 which share the receptors CCR1 and CCR5 with CCL3 and present a similar kinetics of expression than CCL3 (Repeke et al, 2010). Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES/CCL5) is found in greater levels in active periodontal lesions compared to inactive sites (Gamonal et al, 2001, Gemmell et al, 2001) and it chemoattracts lymphocytes and monocytes as well as other cell types (Koch et al, 2005, Schall et al, 1990.…”

The interconnected role of chemokines and estrogen in bone metabolism

“…Mechanical loading, such as orthodontic force, up-regulated the expression of CCL3 and CCR1 in alveolar bone and soft periodontal tissues, thus affecting the recruitment, differentiation, and activation of OC precursor cells and OBs and resulting in bone remodeling (58,77). However, CCL3 had no effect on bone loss associated with periodontal disease (78). CCR5 is another receptor for CCL3 and is related to up-regulation of infection-related bone loss in periodontal disease and the prevention of bone resorption induced by mechanical loading (79,80).…”