Protective effects of cilengitide on inflammation in chondrocytes under excessive mechanical stress.

Chondrocytes constantly receive external stimuli, which regulates remodeling. An optimal level of mechanical stress is essential for maintaining chondrocyte homeostasis, however, excessive mechanical stress induces inflammatory cytokines and protease, such as matrix metalloproteinases (MMPs). Therefore, excessive mechanical stress is considered to be one of the main causes to cartilage destruction leading to osteoarthritis (OA). Integrins are well-known as cell adhesion molecules and act as receptors for extracellular matrix (ECM), and are believed to control intracellular signaling pathways both physically and chemically as a mechanoreceptor. However, few studies have focused on the roles and functions of integrins in inflammation caused by excessive mechanical stress. In this study, we examined the relationship between integrins (αVß3 and αVß5) and the expression of inflammatory factors under mechanical loading in chondrocytes by using an integrin receptor antagonist (cilengitide). Cilengitide suppressed the gene expression of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and MMP-13 induced by excessive mechanical stress. In addition, the protein expression of IL1-ß and MMP-13 was also inhibited by the addition of cilengitide. Next, we investigated the involvement of intracellular signaling pathways in stress-induced integrin signaling in chondrocytes by using western blotting. The levels of p-FAK, p-ERK, p-JNK, and p-p38 were enhanced by excessive mechanical stress and the enhancement was suppressed by treatment with cilengitide. In conclusion, this study revealed that excessive mechanical stress may activate integrins αVß3 and αVß5 on the surface of chondrocytes and thereby induce an inflammatory reaction by upregulating the expression of IL-1ß, TNF-α, MMP-3, and MMP-13 through phosphorylation of FAK and MAPKs.

Effects of Neodymium-Doped Yttrium Aluminium Garnet (Nd:YAG) Laser Irradiation on Bone Metabolism During Tooth Movement.

INTRODUCTION: The aim of this study is to evaluate the effects of low-level neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation on orthodontic tooth movement and histological examination. METHODS: Eleven male Wistar rats (aged 10 weeks) were included. To produce experimental tooth movement in rats, 10 g force was applied to maxillary first molars with nickel titanium closed coil springs. Right molars were irradiated with Nd:YAG laser on days 0, 1, 2, 3, 7, 10, 14, 17, 21 and 24, while un-irradiated left molars were used as control. Distance between mesial side of second molar and distal side of first molar was measured on µCT image during tooth movement and the rats were sacrificed 4 weeks after the initiation of tooth movement. RESULTS: The amount of tooth movement was significantly greater in the irradiation group (0.20 ± 0.06) than in the control group (0.14 ± 0.03) during the first week (P < 0.05). However, no statistically significant difference was found afterwards. There was a tendency of higher tartrate-resistant acid phosphatase (TRAP)-positive nuclei count in the pressure zones of the laser irradiation group, but it was not statistically significant. In immuno-histological examination, expressions of alkaline phosphatase (ALP) and receptor activator of nuclear factor kappa-B ligand (RANKL) were higher at the pressure site of the laser irradiation group than the control group, whereas there was no difference in osteoprotegerin (OPG) expression. CONCLUSION: The results suggest that low-level Nd:YAG laser may stimulate osteoclast and osteoblast activation and accelerate bone metabolism during tooth movement.