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Purpose:This study examined the mechanisms of osteoclast-mediated bone invasion in a model of oral squamous cell carcinoma (OSCC). C3H/HeN mice were inoculated with SCC VII cells into the masseter region to establish an animal model of mandibular invasion by OSCC. Experimental Design:The mice were divided into three groups: a control group, given daily s.c. injections of saline; group 1, given 2 Ag per mouse per day of the bisphosphonate YM529; and group 2, given 10 Ag per mouse per day of YM529. After 3 weeks of treatment, the lesions were studied by micro-computed tomography. After tartrate-resistant acid phosphatase (TRAP) staining, the osteoclasts were easily identified, and the percentages of the area occupied by osteoclasts were calculated by computer for each sample. The tumors were analyzed by RT-PCR to determine the mRNA expression of interleukin-6 (IL-6), parathyroid hormone^related protein (PTHrP), tumor necrosis factor-a (TNF-a), receptor activator of nuclear factor-nB (RANK), RANK ligand (RANKL), and osteoprotegerin. Results: SCC VII cells rapidly multiplied in the masseter muscle of the mice. Bone invasion was evident only in the control group on micro-computed tomography. On TRAP-stained slices, the percentages of osteoclasts in groups 1 and 2 were significantly lower than that in the control group. The mRNA expressions of IL-6, PTHrP,THF-a, and RANK decreased as the concentration of YM529 increased. Conclusions: We conclude that various cancer-derived cytokines play important roles in the invasion of bone by OSCC. YM529, a third-generation bisphosphonate, can suppress osteoclastmediated bone invasion by OSCC. The mechanism of this effect might involve inhibition of cytokines such as IL-6, PTHrP,TNF-a, and RANK byYM529.

This study aimed to evaluate the effi cacy of rabbit demineralized dentin matrix (DDM) as a recombinant human bone morphogenetic protein-2 (rhBMP-2) carrier using the subcutaneous tissues of mice and rabbit calvarial critical-sized defects. DDM of rabbit, combined with rhBMP-2 (DDM/rhBMP-2) was transplanted into the subcutaneous tissues of 6 mice and 6 rabbit calvarial critical-sized defects (DDM = 0.03 g, control; DDM/rhBMP-2 = 0.03 g of DDM, 0.2 mg/ml, 5.0 μg of rhBMP-2, experimental). Both DDM and DDM/rhBMP-2 was transplanted into the left and right subcutaneous tissues of mice symmetrically. For rabbits, 4 round critical-sized defects (8 mm diameter) were formed on the exposed skull. DDM was transplanted into the 2 defects on the left sides (n = 12) and DDM/rhBMP-2 into the right sides (n = 12). Two animals among 6 mice and 6 rabbits were sacrifi ced respectively at the 1, 2, and 4 experimental weeks for the histological and histomorphometrical evaluations with hematoxylin and eosin staining. Tissues from rabbits were imaged via micro-computed tomography (μCT). DDM/rhBMP-2 in mice induced new bone formation at 2 weeks and maturation with bone marrow at 4 weeks. DDM/rhBMP-2 in rabbit calvarium induced new bone formation remarkably at 4 weeks 21.77-47.99% compared to the DDM. These observations suggest that DDM could be considered a potential carrier of rhBMP-2. The rhBMP-2 loaded on DDM enhanced bone formation.

Objectives This study aimed to quantitatively compare the somatosensory function changes of inferior alveolar nerve (IAN) after mandibular third molar extraction with a surgery protocol of coronectomy, as opposed to the conventional method. Materials and methods Patients with a lower third molar directly contacting IAN were recruited and assigned either to a test group (coronectomy group) or a control group (conventional extraction). A standardized quantitative sensory testing (QST) battery was performed for four times: one week before surgery and the second, seventh, and 28th days after surgery. Z-scores and the loss/gain coding system were applied for each participant. Results A total of 140 molars (test group: n = 91, control group: n = 49) were enrolled. The sensitivity of the mechanical detection threshold (MDT) and pressure pain threshold (PPT) significantly increased after surgery more than before surgery in both groups (P ≤ 0.001). After the surgery, the sensitivities of the cold detection threshold (CDT), cold pain threshold (CPT), and heat pain threshold (HPT) were significantly higher in the test group than in the control group (P ≤ 0.027). The risk of IANI was significantly larger (P = 0.041) in the test group than in the control group. Conclusions QST was a sensitive way to detect somatosensory abnormalities even with no subjective complaint caused by surgery. Coronectomy had less influence on IAN function than conventional total extraction. Clinical relevance The somatosensory function changes after mandibular third molar extraction were quantitatively studied, and coronectomy was proved a reliable alternation to reduce IAN injury rate.

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Abstract. the aim of this study was to examine the value of osteoclast-related cytokines in biopsy specimens for predicting mandibular invasion by oral squamous cell carcinoma (OScc). in this retrospective study, biopsy specimens were obtained from 30 patients with OScc. We observed the expression of seven osteoclast-related cytokines (il-1α, ranKl, pthrp, OpG, il-6, ranK and tnF-α) using immunohistochemical (ihc) staining and of an osteoclast using tartrate-resistant acid phosphatase (trap) staining. the results were as follows: i) double-staining and ihc staining for ranKl, pthrp and il-1α in biopsy samples had diagnostic potential for predicting mandibular invasion; ii) trap-positive monoor multinuclear cells were noted in the biopsy samples; iii) double-positive or -negative findings appeared to reliable indicate whether samples were invasion-positive or invasionnegative. positive ihc staining for pthrp, il-1α or ranKl appeared to typically indicate an invasion-positive lesion. We suggest that the expression of both osteoclasts and osteoclastrelated cytokines can be used to predict mandibular invasion.

We explored the feasibility and efficacy of a degradable magnesium (Mg) alloy guided bone regeneration (GBR) in the treatment of bone defects after tooth extraction. A GBR membrane (MAR-Gide (MG)) was used to treat a mandibular second molar (M2M)-distal bone defect (DBD). In eight beagle dogs, bilateral mandibular second and fourth premolars were hemi-sected. The distal roots were removed to create a two-wall bony defect of dimension 5 mm × 5 mm × 5 mm to simulate M2M-DBD. Thirty-two bone defects were assigned randomly into four groups according to GBR membranes (MG and Bio-Gide (BG)) applied and the time of killing (3 months and 6 months after surgery). The osteogenesis of bone defects and MG degradation were analyzed using micro-CT, histology (staining, tartrate-resistant acid phosphatase), and inductively coupled plasma mass spectrometry. MG did not increase the prevalence of infection, wound dehiscence, or subcutaneous emphysema compared with those using BG. Trabecular volume/total volume at 3 months (63.71 ± 10.4% vs. 59.97 ± 8.94%) was significantly higher in the group MG than that in the group BG. Implanted MG was degraded completely within 3 months, and “island-shaped” new bone was found near MG degradation products. A significant difference was not found in vertical bone height or percent of new bone formation (45.44 ± 12.28% vs. 43.49 ± 7.12%) between the groups. The concentration of rare-earth elements in mandibular lymph nodes of the group MG was significantly higher than that of the group BG ( P ≤ 0.017 ) but did not lead to histopathological changes. In summary, MG exhibited good biocompatibility and clinical applicability compared with BG in vivo. The osteogenic effect of MG could be enhanced by regulating the degradation rate of Mg-alloy.

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