The effect of CCL3 and CCR1 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice.
Bone remodeling is affected by mechanical loading and inflammatory mediators, including chemokines. The chemokine (C-C motif) ligand 3 (CCL3) is involved in bone remodeling by binding to C-C chemokine receptors 1 and 5 (CCR1 and CCR5) expressed on osteoclasts and osteoblasts. Our group has previously demonstrated that CCR5 down-regulates mechanical loading-induced bone resorption. Thus, the present study aimed to investigate the role of CCR1 and CCL3 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice. Our results showed that bone remodeling was significantly decreased in CCL3(-/-) and CCR1(-/-) mice and in animals treated with Met-RANTES (an antagonist of CCR5 and CCR1). mRNA levels of receptor activator of nuclear factor kappa-B (RANK), its ligand RANKL, tumor necrosis factor alpha (TNF-α) and RANKL/osteoprotegerin (OPG) ratio were diminished in the periodontium of CCL3(-/-) mice and in the group treated with Met-RANTES. Met-RANTES treatment also reduced the levels of cathepsin K and metalloproteinase 13 (MMP13). The expression of the osteoblast markers runt-related transcription factor 2 (RUNX2) and periostin was decreased, while osteocalcin (OCN) was augmented in CCL3(-/-) and Met-RANTES-treated mice. Altogether, these findings show that CCR1 is pivotal for bone remodeling induced by mechanical loading during orthodontic tooth movement and these actions depend, at least in part, on CCL3.
Laboratory Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, ICB/UFMG, Avenida Presidente Antônio Carlos 6627, 31.270-9010, Belo Horizonte, MG, Brazil. silvana.albuquerque@gmail.com
Silvana R de Albuquerque
SR
Taddei
Celso M
CM
Queiroz-Junior
Adriana P
AP
Moura
Ildeu
I
Andrade
Gustavo P
GP
Garlet
Amanda E I
AE
Proudfoot
Mauro M
MM
Teixeira
Tarcília A
TA
da Silva
D000818:Animals; D001483:Base Sequence; D001696:Biomechanical Phenomena; D016723:Bone Remodeling / Q000502:physiology*; D054405:Chemokine CCL3 / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D054389:Receptors, CCR1 / Q000235:genetics / Q000502:physiology*; D014087:Tooth Movement Techniques
C496534:Ccl3 protein, mouse; C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D017931:DNA Primers; D054389:Receptors, CCR1