Browsing by Subject "OSTEOCLASTS"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Microbe-Dependent Exacerbated Alveolar Bone Destruction in Heterozygous Cherubism Mice
    (American Society for Bone and Mineral Research, 2020-02-24) Kittaka, Mizuho; Yoshimoto, Tetsuya; Schlosser, Collin; Kajiya, Mikihito; Kurihara, Hidemi; Reichenberger, Ernst J.; Ueki, Yasuyoshi; Biomedical Sciences and Comprehensive Care, School of Dentistry
    Cherubism (OMIM#118400) is a craniofacial disorder characterized by destructive jaw expansion. Gain‐of‐function mutations in SH3‐domain binding protein 2 (SH3BP2) are responsible for this rare disorder. We have previously shown that homozygous knock‐in (KI) mice (Sh3bp2 KI/KI) recapitulate human cherubism by developing inflammatory lesions in the jaw. However, it remains unknown why heterozygous KI mice (Sh3bp2 KI/+) do not recapitulate the excessive jawbone destruction in human cherubism, even though all mutations are heterozygous in humans. We hypothesized that Sh3bp2 KI/+ mice need to be challenged for developing exacerbated jawbone destruction and that bacterial stimulation in the oral cavity may be involved in the mechanism. In this study, we applied a ligature‐induced periodontitis model to Sh3bp2 KI/+ mice to induce inflammatory alveolar bone destruction. Ligature placement induced alveolar bone resorption with gingival inflammation. Quantification of alveolar bone volume revealed that Sh3bp2 KI/+ mice developed more severe bone loss (male: 43.0% ± 10.6%, female: 42.6% ± 10.4%) compared with Sh3bp2 +/+ mice (male: 25.8% ± 4.0%, female: 30.9% ± 6.5%). Measurement of bone loss by the cement‐enamel junction–alveolar bone crest distance showed no difference between Sh3bp2 KI/+ and Sh3bp2 +/+ mice. The number of osteoclasts on the alveolar bone surface was higher in male Sh3bp2 KI/+ mice, but not in females, compared with Sh3bp2 +/+ mice. In contrast, inflammatory cytokine levels in gingiva were comparable between Sh3bp2 KI/+ and Sh3bp2 +/+ mice with ligatures. Genetic deletion of the spleen tyrosine kinase in myeloid cells and antibiotic treatment suppressed alveolar bone loss in Sh3bp2 KI/+ mice, suggesting that increased osteoclast differentiation and function mediated by SYK and accumulation of oral bacteria are responsible for the increased alveolar bone loss in Sh3bp2 KI/+ mice with ligature‐induced periodontitis. High amounts of oral bacterial load caused by insufficient oral hygiene could be a trigger for the initiation of jawbone destruction in human cherubism.
  • Thumbnail Image
    Item
    ROLE OF OSTEOCLASTS IN THE BIOCORROSION OF METAL IMPLANTS
    (Office of the Vice Chancellor for Research, 2011-04-08) Theriac, Haili; Dodge, Todd; Largura, Heather; Hara, A.; Liu, S.; Bruzzaniti, Angela
    Mini implants (MIs), typically composed of stainless steel (SS) or titanium alloy (Ti), have recently emerged as superior alternatives to traditional dental and orthopedic implants. When a metal implant is inserted into bone, a process called bone remodeling is triggered near the implant. Bone remodeling involves the activity of osteoblasts (OBs), which produce new bone tissue, and osteoclasts (OCs), which degrade and digest bone. OCs degrade bone by acidifying the extracellular environment and secreting hydrolytic enzymes that degrade the extracellular matrix. However, the acidification of the extracellular environment can potentially lead to the biological corrosion of metal implants after implantation. This may have important consequences such as cell toxicity, decreased osseointegration of the implant, and implant loosening. The objective of this study is to determine if implants made from Ti are more resistant to OC-mediated biocorrosion than stainless steel (SS) implants. We hypothesize that biocorrosive activity by OCs will be greater on SS than titanium. To assess the biocorrosive effects of OCs on SS and Ti, the top face of 150 µm thick sections of each metal were scanned using a Proscan 2000 Scantron to provide accurate three dimensional surface measurements of the metals before introduction of OCs. OC precursors were isolated from the bone marrow of C57/bl6 mice and differentiated with macrophage colony stimulating factor and receptor activator of NF-kappaB ligand for 7 days in the presence of either SS or Ti metals. The metals discs were then removed and rescanned with the Proscan Scantron and changes in the surface measurements before and after OC growth was calculated. OCs were fixed and stained for tartrate-resistant acid phosphatase, a marker of mature OCs, and counted. Our preliminary findings revealed that the surface roughness of SS was reduced to a greater extent than Ti metals. OC number was also reduced in cultures containing SS compared with Ti. These findings suggest SS may be more susceptible to OC-mediated biocorrosion than Ti-based metal implants. Although the physiological implications are unclear, we speculate that sustained corrosion of SS can negatively affect the long-term stability of implants in vivo.