Bisphosphonate treatment increases the size of the mandibular condyle and normalizes growth of the mandibular ramus in osteoprotegerin-deficient mice.

Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor family which plays a crucial role in negative regulation of osteoclastic bone resorption. OPG-deficient (OPG-/-) mice develop severe osteoporosis caused by significant enhancement of bone resorption by osteoclasts. We investigated the effect of administering bisphosphonate on mandibular growth and development in OPG-/- mice. Eight-week-old male OPG-/- mice and wild-type (WT) mice were administered bisphosphonate (1.25 mg/kg body weight) intraperitoneally once every 3 days for 30 days. All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG-/- mice with bisphosphonate than in those without bisphosphonate. The volume of the whole condyle and the mandibular length in OPG-/- mice without bisphosphonate were significantly smaller than in WT mice without bisphosphonate. Bisphosphonate treatment of the OPG-/- mice resulted in an increase in the volume of the mandibular condyle and mandibular ramus length. In fact, the mandibular ramus length in OPG-/- mice with bisphosphonate was similar to the length in WT mice without bisphosphonate. Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG-/- mice without bisphosphonate tended to be less marked in the OPG-/- mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG-/- mice with bisphosphonate than in those without bisphosphonate. In conclusion, bisphosphonate treatment results in an increase in mandibular condylar dimensions and normalization of mandibular ramus growth.

The effect of superficial chemistry of titanium on osteoblastic function.

The surface topography and chemistry of titanium are postulated to be two major factors that affect the osseointegration capacity of titanium implants. However, it is extremely difficult to control one factor without changing the other, which prevents the isolation of the genuine effect of one factor. This study aimed to determine whether surface chemistry of titanium alone affects osteoblastic function. Two different titanium surfaces were prepared by sputter depositioning of titanium (Ti; 99.99% purity) or titanium dioxide (TiO2; 99.99% purity) (50-nm thick for each) onto machined commercially pure titanium disks. Rat bone marrow-derived osteoblastic cells were cultured on each of the two surfaces. TiO2 surface showed 4.4 times higher elemental oxygen concentration and higher water wettability than Ti surface. Scanning electron microscopic and atomic force microscopic examination revealed no differences in surface topography and roughness values between the two surfaces. The cell proliferated more on TiO2 than on Ti by up to 60%. Although the expression of collagen I gene increased more rapidly on TiO2 at early culture stage of day 3, the late stage marker genes for osteoblastic differentiation, including osteopontin and osteocalcin, were not modulated between the two cultures. The alkaline phosphatase positive area and mineralized nodule area were approximately two times larger on TiO2 than on Ti. In conclusion, titanium materials having different superficial chemistry, that is, titanium or titanium dioxide, may exert different biological capacity of osteoblasts; titanium dioxide may induce superior osteoconduction, primarily because of the increased osteoblastic proliferation.

Proliferation and differentiation of rat bone marrow stromal cells on poly(glycolic acid)-collagen sponge.

We studied the effects of dexamethasone (Dex) and basic fibroblast growth factor (bFGF) on proliferation and differentiation of rat bone marrow stromal cells (RBMSCs), using three scaffolds: collagen sponge, poly(glycolic acid) (PGA)-collagen sponge, and PGA-collagen (UV) sponge. RBMSCs were seeded into the sponges, and cultured in primary medium, primary medium with Dex, and primary medium with bFGF and Dex. Three weeks after cultivation, we examined alkaline phosphatase (ALP) activity and cell number in the sponges, and also performed macroscopic, light microscopic, and scanning electron microscopic (SEM) observations. Collagen sponge shrank considerably, but PGA-collagen and PGA-collagen (UV) sponges maintained most of their original shape. PGA-collagen (UV) sponge supplemented with bFGF and Dex together had the highest ALP activity and cell number, followed by PGA-collagen sponge. Although collagen sponge showed cell proliferation only on the surface, the other two sponges showed cell proliferation in the interior. SEM showed the best cell attachment to PGA-collagen (UV) sponge in the presence of bFGF and Dex, followed by PGA-collagen sponge. In conclusion, PGA-collagen (UV) and PGA-collagen sponges proved to be much more useful as scaffolding for bone regeneration when combined with bFGF and Dex.

Effect of tensile force on the expression of IGF-I and IGF-I receptor in the organ-cultured rat cranial suture.

Insulin-like growth factors (IGFs) play an important role in the regulation of bone metabolism. In this study, we investigated changes in the expression of IGF-I and IGF-I receptor and cell proliferation when a continuous tensile force was applied to the cranial suture of cultured rat calvaria. The parietal bones with the midsagittal suture were removed from male Wistar rats (19-days old), cultured for 24h, and divided into two groups. In the experimental group, tensile force (3 x 10(-3)N) was applied by helical springs to the midsagittal suture, whereas helical springs with no tension (0 N) were set in the control group. The tensile force significantly increased the expression of both IGF-I mRNA and protein (P < 0.05). By using in situ hybridisation, we also confirmed that IGF-I and IGF-I receptor mRNAs were localized in osteoblast-like and fibroblastic cells subjected to the tensile force. Also, this force stimulated the proliferation of osteoblast-like and fibroblastic cells in calvaria, without affecting their alkaline phosphatase activity. These results indicate that a tensile force applied to a cranial suture can cause an increase in the production of IGF-I and IGF-I receptors in osteoblast-like and fibroblastic cells, and this increase in IGF-I may cause the proliferation of the cells in an autocrine or paracrine manner.

[Human papillomavirus infection in the oral cavity of denture wearers].

PURPOSE: The purpose of this study was to determine the frequency of human papillomavirus(HPV)infections in the oral cavity of middle-aged and elderly dental patients with dentures. METHODS: In this study, 47 patients (20 men and 27 women), aged from 50 to 78 years, were randomly selected from the patients in the Department of Prosthodontics, Aichi-Gakuin University Affiliated Dental Hospital. Oral squamous cells were collected from swabs of the buccal mucosa. For this procedure, informed consent was obtained. Extracted DNA was evaluated for HPV infections by PCR methods, using consensus and specific primers, and direct DNA sequencing analysis. RESULTS: Twenty-four of 47 specimens (51.1%) were positive for HPV DNA. A statistically significant association was not found in the HPV positivity between men and women. The high rate of infection was recognized from 60 or more years old. A statistically significant association was found in the HPV positivity between non-denture wearers and denture wearers. Frequent HPV types in the specimens of all were HPV11, 4 and 16. Frequent HPV types in the specimens of non-denture wearers and denture wearers were HPV4, 11 and HPV11, 16 and 4, respectively. CONCLUSIONS: The results of the present investigation indicate that HPV is present in the oral cavity, especially those of denture wearers, of middle-aged and elderly patients. It is suggested, therefore, that the oral cavity of middle-aged and elderly patients with dentures is a reservoir of HPVs where later HPV-associated diseases, such as oral cancer and other oral lesions, may develop.

Effect of methotrexate-induced neutropenia on pulpal inflammation in rats.

The purpose of this study was to determine the role of neutropenia in pulpal inflammation. We investigated the effect of methotrexate-induced neutropenia on pulpal inflammation in rats. Pulpal inflammation was produced by pulpal exposure. Thirty-six rats were divided equally into control and experimental groups. The control animals received no injection, whereas the experimental animals were injected with 7.5 mg/kg of methotrexate once a day for 3 days before the pulpal exposure. The pulp was exposed in the mandibular first molar of all animals, and the exposed areas were left open. Animals were killed at 2, 4, and 7 days thereafter. Before they were killed, peripheral blood was taken. The number of total leukocytes and neutrophils in the peripheral blood of experimental animals was significantly decreased compared with those of control animals. The methotrexate-induced neutropenia resulted in the initiation of a bacterial invasion into the pulpal tissue and an increase in pulpal necrosis, as well as lessened abscess formation. Histometrically, the area of pulpal necrosis in experimental animals was significantly greater than that in the control animals. Immunohistochemically, the neutropenia resulted in inhibition of the infiltration by neutrophils. These results suggest that the neutrophil plays an important role in the defense against bacteria in pulpal tissue.