No abstract

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.