An M-CSF Receptor c-Fms Antibody Inhibits Mechanical Stress-Induced Root Resorption during Orthodontic Tooth Movement in Mice
ABSTRACT To examine the effect of anti-c-Fms antibody on odontoclastogenesis and root resorption in an orthodontic tooth movement mouse model.
We used orthodontic tooth movement in which an Ni-Ti coil spring was inserted between the upper incisors and the upper first molar. Root resorption occurred in this model. Anti-c-Fms antibody was injected daily into a local site for 12 days during mechanical loading. Odontoclastogenesis and root resorption were assessed by histology and scanning electron microscopy.
The anti-c-Fms antibody significantly inhibited odontoclastogenesis and root resorption during orthodontic tooth movement.
M-CSF and/or its receptor is a potential therapeutic target in mechanical stress- induced odontoclastogenesis, and injection of an anti-c-Fms antibody might be useful for inhibition of mechanical stress-induced root resorption during orthodontic tooth movement.
- SourceAvailable from: Hideki Kitaura
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- "In our mouse orthodontic tooth movement system, a Ni-Ti coil spring was inserted between the upper incisors and the upper first molar. Root resorption occurred in this model . Root resorption results from the activity of odontoclasts, which play a role similar to that of osteoclasts in bone resorption. "
ABSTRACT: Mechanical force loading exerts important effects on the skeleton by controlling bone mass and strength. Several in vivo experimental models evaluating the effects of mechanical loading on bone metabolism have been reported. Orthodontic tooth movement is a useful model for understanding the mechanism of bone remodeling induced by mechanical loading. In a mouse model of orthodontic tooth movement, TNF- α was expressed and osteoclasts appeared on the compressed side of the periodontal ligament. In TNF-receptor-deficient mice, there was less tooth movement and osteoclast numbers were lower than in wild-type mice. These results suggest that osteoclast formation and bone resorption caused by loading forces on the periodontal ligament depend on TNF- α . Several cytokines are expressed in the periodontal ligament during orthodontic tooth movement. Studies have found that inflammatory cytokines such as IL-12 and IFN- γ strongly inhibit osteoclast formation and tooth movement. Blocking macrophage colony-stimulating factor by using anti-c-Fms antibody also inhibited osteoclast formation and tooth movement. In this review we describe and discuss the effect of cytokines in the periodontal ligament on osteoclast formation and bone resorption during mechanical force loading.The Scientific World Journal 01/2014; 2014:617032. DOI:10.1155/2014/617032 · 1.73 Impact Factor
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ABSTRACT: We studied two rhesus monkeys before and after surgical ablation of the nodulus and uvula (Nod/Uv) of the cerebellum. Three-axis eye movements were recorded with the magnetic-field scleral search coil system during a variety of vestibular and ocular motor tasks. Here we describe the effects of the Nod/Uv lesions on dynamic (head translation) and static (head tilt) otolith-mediated vestibulo-ocular reflexes. The main findings were: 1. eye velocity during sinusoidal vertical translation (1.5 Hz) was reduced by 59% in the dark and 36% in the light; 2. eye velocity during steps of horizontal translation was reduced, but only in the dark and more so during the sustained (constant velocity) than the initial (acceleration) part of the response, and 3. there was a torsional nystagmus that depended on the position of roll head tilt, but static ocular counterroll was unchanged. These results suggest new roles for the Nod/Uv in the processing of otolith signals. This is likely important not only for facilitating gaze during linear head motion, but also for maintaining postural stability and one's orientation relative to gravity. The lesions appeared to have a greater effect on responses to vertical motion, particularly in the light (in contrast, responses to interaural translation in the light were nearly normal), suggesting a particular importance of the Nod/Uv in processing signals arising from the sacculi.Progress in brain research 02/2008; 171:167-72. DOI:10.1016/S0079-6123(08)00622-5 · 5.10 Impact Factor
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ABSTRACT: Little is known about the effects of mechanical forces on osteoclastogenesis by bone marrow macrophages (BMMs) in the absence of mechanosensitive cells, including osteoblasts and fibroblasts. In this study, we examined the effects of mechanical force on osteoclastogenesis by applying centrifugal force to BMMs using a horizontal microplate rotor. Our findings, as measured by an in vitro model system, show that tumor necrosis factor (TNF)-α is capable of inducing osteoclast differentiation from BMMs and bone resorption in the presence of macrophage-colony stimulating factor (M-CSF) and is further facilitated by receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). Application of force to BMMs accelerated TNF-α-induced osteoclastogenesis; this was inhibited either by anti-TNF-α or anti-TNF-α receptor but not by OPG. TNF-α also increased c-Fms expression at both mRNA and protein levels in BMMs. An anti-c-Fms antibody completely inhibited osteoclast differentiation and bone resorption induced by TNF-α but partially blocked osteoclastogenesis stimulated in combination with RANKL. These results suggest that TNF-α (in the presence of M-CSF) is capable of inducing osteoclastogenesis from BMMs, and that osteoclastogenesis is significantly stimulated by force application through the activation of c-Fms-mediated signaling. Overall, the present study reveals the facilitating effect of mechanical force on osteoclastic differentiation from BMMs without the addition of mechanosensitive cells.Journal of Cellular Biochemistry 12/2010; 111(5):1260-9. DOI:10.1002/jcb.22849 · 3.37 Impact Factor