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woven bone [keywords]
- Preservation of a tooth related with central giant cell granuloma with non-invasive curettage: 7 years followed-up case report. [Journal Article]
- Oral Health Dent Manag 2014 Sep; 13(3):634-7.
Central Giant Cell Granuloma (CGCG) is defined by the World Health Organization as an intraosseous lesion consisting of cellular fibrous tissue containing multiple foci of hemorrhage, aggregations of multinucleated giant cells, and occasionally trabeculae of woven bone. An 8-year-old patient presented with painless swelling and bleeding in his upper right canine region was referred to our clinic. Incisional biopsy was confirmed that this was a CGCG. The patient was treated with non-invasive curettage and secondary intention healing. Seven-year follow-up of the patient revealed a complete resolution of the lesion and uneventful eruption of the permanent canine tooth. In this case report, a successful long-term outcome of the conservative treatment of the CGCG was presented.
- Novel EP4 receptor agonist-bisphosphonate conjugate drug (C1) promotes bone formation and improves vertebral mechanical properties in the ovariectomized rat model of postmenopausal bone loss. [JOURNAL ARTICLE]
- J Bone Miner Res 2014 Oct 4.
Current treatments for postmenopausal osteoporosis aim to either promote bone formation or inhibit bone resorption. The C1 conjugate drug represents a new treatment approach by chemically linking the anti-resorptive compound alendronate (ALN) with the anabolic agent prostanoid EP4 receptor agonist (EP4a) through a linker molecule (LK) to form a conjugate compound. This enables the bone-targeting ability of ALN to deliver EP4a to bone sites and mitigate the systemic side effects of EP4a, while also facilitating dual anti-resorptive and anabolic effects. In vivo hydrolysis is required to release the EP4a and ALN components for pharmacological activity. Our study investigated the in vivo efficacy of this drug in treating established bone loss using an ovariectomized (OVX) rat model of postmenopausal osteopenia. In a curative experiment, 3-month-old female Sprague-Dawley rats were OVX, allowed to lose bone for 7 weeks, then treated for 6 weeks. Treatment groups consisted of C1 conjugate at low and high doses, vehicle-treated OVX and sham, prostaglandin E2 (PGE2 ), and mixture of unconjugated ALN-LK and EP4a to assess the effect of conjugation. Results showed that weekly administration of C1 conjugate dose-dependently increased bone volume in trabecular bone, which partially or completely reversed OVX-induced bone loss in the lumbar vertebra and improved vertebral mechanical strength. The conjugate also dose-dependently stimulated endocortical woven bone formation and intracortical resorption in cortical bone, with high dose treatment increasing the mechanical strength but compromising the material properties. Conjugation between the EP4a and ALN-LK components was crucial to the drug's anabolic efficacy. To our knowledge, the C1 conjugate represents the first time that a combined therapy using an anabolic agent and the anti-resorptive compound ALN has shown significant anabolic effects which reversed established osteopenia. © 2014 American Society for Bone and Mineral Research.
- Defective bone repair in mast cell deficient mice with c-Kit loss of function. [Journal Article, Research Support, Non-U.S. Gov't]
- Eur Cell Mater 2014.:209-21; discussion 221-2.
KitW-sh mice carry an inactivating mutation in the gene encoding the receptor for stem cell factor, which is expressed at high levels on the surface of haematopoietic precursor cells. The mutation results in mast cell deficiency, a variety of defects in innate immunity and poorly defined abnormalities in bone. The present study was designed to characterise healing of a cortical window defect in skeletally mature KitW-sh mice using high-resolution micro computed tomographic imaging and histological analyses. The cortical bone defect healed completely in all wild type mice but failed to heal in about half of the KitW-sh mice by 12 weeks post-operative. Defective healing was associated with premature and excessive expression of TRAP positive cells embedded in fibrous marrow but with little change in ALP activity. Immuno-histochemical analyses revealed reduced CD34 positive vascular endothelial cells and F4/80 positive macrophages at 1 and 2 weeks post-operative. Impaired bone healing in the KitW-sh mice was therefore attributed to altered catabolic activity, impaired re-vascularisation and compromised replacement of woven with compact bone.
- Transplantation of stem cells from human exfoliated deciduous teeth for bone regeneration in the dog mandibular defect. [Journal Article]
- World J Stem Cells 2014 Sep 26; 6(4):505-10.
To investigate the effect of stem cells from human exfoliated deciduous teeth (SHED) transplanted for bone regeneration in the dog mandibular defect.In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-and-through defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level.There were no significant differences between control and SHED-seeded groups in connective tissue (P = 0.248), woven bone (P = 0.248) and compact bone (P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period.SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs.
- A clinico-pathologic review of 56 cases of ossifying fibroma of the jaws with emphasis on the histomorphologic variations. [Journal Article]
- Niger J Clin Pract 2014 Sep-Oct; 17(5):619-23.
This study aims at contributing to the definitive diagnosis of ossifying fibroma (OF) based on histomorphological features. The study also aims to determine some demographic features of OF, common sites of occurrence and to determine whether behavior correlates well with the histomorphological variations seen in the lesion.A total of 80 patients who were diagnosed either as cementifying fibroma CF, OF and cemento-ossifying fibroma (COF) of the jaws from the files of the Oral Pathology Department of the University of the Witwatersrand Dental School were retrieved and the histology slides of each case were reviewed with the most recent diagnostic criteria for OF and the authors additional criteria. A total of 56 cases that met the set criteria were analyzed.The patients were clustered within the third and fourth decades of life ( n = 39, 69.6%). Majority of the patients were black (83.93%), whereas the rest were whites (12.50%) and Asians (3.57%). There were 17 males (30.4%) and 39 females (69.6%), giving a male to female ratio of 1:2.3. Most of the lesions (70.3%) occurred in the mandible, involving the premolar molar region (56.7%). Scanty fibrous tissues in highly cellular lesions were found in 36 (64.3%) of the cases. There were globular, dystrophic or granular calcifications mixed with irregularly shaped trabeculae of lamellar or cellular woven bone or osteoid were found, in 36 (64.3%) cases.Demographic data, clinicoradiologic features, combined with histopathology will continue to be relevant in the definitive diagnosis of OF and in predicting its behavior. Highly aggressive lesions with shorter duration in people below 15 years were called juvenile OF and treated as such, while OF applies to other conventional ones.
- Stk11 (Lkb1) deletion in the osteoblast lineage leads to high bone turnover, increased trabecular bone density and cortical porosity. [JOURNAL ARTICLE]
- Bone 2014 Sep 18.:98-108.
The mTOR pathway couples energy homeostasis to growth, division and survival of the cell. Stk11/Lkb1 is a critical serine-threonine protein kinase in the inhibition of mTOR pathway action. In the mammalian skeleton, Stk11 regulates the transition between immature and hypertrophic chondrocytes. Here, we have focused on the action of Stk11in the osteoblast lineage through osteoblast specific-removal of Stk11 activity. In the mouse model system, specification and primary organization of the neonatal boney skeleton is independent of Stk11. However, histological, molecular and micro-CT analysis revealed a marked perturbation of normal bone development evident in the immediate post-natal period. Cortical bone was unusually porous displaying a high rate of turnover with new trabeculae forming in the endosteal space. Trabecular bone also showed enhanced turnover and marked increase in the density of trabeculae and number of osteoclasts. Though mutants showed an expansion of bone volume and trabecular number, their bone matrix comprised large amounts of osteoid and irregularly deposited woven bone highlighted by diffuse fluorochrome labeling. Additionally, we observed an increase in fibroblast-like cells associated with trabecular bone in Stk11 mutants. Stk11 down-regulates mTORC1 activity through control of upstream modulators of the AMP kinase family: an increase in the levels of the phosphorylated ribosomal protein S6, a target of mTORC1-mediated kinase activity, on osteoblast removal of Stk11 suggests deregulated mTORC1 activity contributes to the osteoblast phenotype. These data demonstrate Stk11 activity within osteoblasts is critical for the development of normally structured bone regulating directly the number and coordinated actions of osteoblasts, and indirectly osteoclast number.
- Peri-implant bone innervation: Histological findings in humans. [Journal Article]
- Eur J Oral Implantol 2014; 7(3):283-92.
The aim of the present study was to describe nerve fibres around osseointegrated implants in humans.Twelve mechanically failed implants, retrieved from 10 patients were collected from three dental centres over a period of 5 years. After implant removal, decalcified semi-thin sections (0.5 μm) were stained with thionic methylene blue for light microscopic analysis. In addition, an ultrastructural analysis was performed on serial ultra-thin sections (0.06 μm) using transmission electron microscopy.Both myelinated and unmyelinated nerve fibres could be identified inside the Haversian canals of the osteonal bone near the implant threads. Myelinated fibres were also located at the woven bone around the implant. However, no differentiated nerve endings could be observed around the implants.This study shows the presence of nerve fibres in human peri-implant bone. Previous studies in animals showed that those fibres participate in the process of bone modelling and remodelling. Yet, the role of peri-implant bone innervation in the osseoperception phenomenon cannot be ruled out since the mechanism of mechanoreception in bone is not fully understood. Conflict of interest statement: The authors declare that there is no conflict of interest.
- Osteocyte expression of caspase-3, COX-2, IL-6 and sclerostin are spatially and temporally associated following stress fracture initiation. [Journal Article]
- Bonekey Rep 2014.:571.
Stress fractures (SFxs) are debilitating injuries and exact mechanisms that initiate their repair incompletely understood. We hypothesised that osteocyte apoptosis and expression of cytokines and proteins such as sclerostin, VEGF, TGF-β, COX-2 and IL-6 were early signalling events to facilitate the formation of periosteal woven bone and recruitment of osteoclast precursors to the site of remodelling. A SFx was created in the right ulna of mature female wistar rats using cyclic end loading. Rats were killed 1, 4 and 7 days after loading (n=5 per group). Standard histological staining was used to examine SFx morphology and immunohistochemistry to detect the localisation of these proteins and in situ hybridisation to detect mRNA along the SFx line or gene expression to quantify the target genes. Unloaded ulnae served as controls. The labelling index of caspase-3, COX-2 and IL-6 was significantly elevated in the region of SFxs at all time points compared with controls (P<0.001). In addition, the labelling index of sclerostin protein was significantly reduced in osteocytes adjacent to the SFx region when compared with controls at all three time points (P<0.001). Both VEGF and TGF-β expressions were only localised in the woven bone. These data reinforce the involvement of osteocyte apoptosis in the healing of fatigue damage in bone, and demonstrate that local regulation of sclerostin, COX-2 and IL-6 are important signalling events associated with new bone formation and SFx remodelling.
- Sensory innervation around immediately vs. delayed loaded implants: a pilot study. [JOURNAL ARTICLE]
- Int J Oral Sci 2014 Sep 12.
Although neurophysiological and psychophysical proof of osseoperception is accumulating, histomorphometric evidence for the neural mechanisms of functional compensation following immediate and delayed implant loading is still lacking. For this randomized split-mouth study, six mongrel dogs randomly received one of four treatment protocols at 36 implant-recipient sites over 16 weeks (third maxillary incisor, third and fourth mandibular premolar): immediate implant placement and immediate loading (IIP+IL); delayed implant placement and delayed loading (DIP+DL); delayed implant placement and immediate loading (DIP+IL); and natural extraction socket healing (control). Histomorphometry was performed in the peri-implant bone and soft tissues within 300 µm around the implants. Immunocytochemistry and transmission electron microscopy were used to confirm the presence of neural structures and to reveal their ultrastructural characteristics, respectively. Myelinated nerve fibres densely populated the peri-implant crestal gingival and apical regions, although they were also identified in the woven bone and in the osteons near the implant threads. Compared with the control group in the mandible, the group that received IIP+IL showed a higher innervation (in N⋅mm(-2), 5.94±1.12 vs. 3.15±0.63, P<0.001) and smaller fibre diameter (in µm, 1.37±0.05 vs. 1.64±0.13, P=0.016), smaller axon diameter (in µm, 0.89±0.05 vs. 1.24±0.10, P=0.009) and g-ratio (0.64±0.04 vs. 0.76±0.05, P<0.001) in the middle region around the implants. Compared with DIP+IL in the mandible, IIP+IL had a higher nerve density (in N⋅mm(-2), 13.23±2.54 vs. 9.64±1.86, P=0.027), greater fibre diameter (in µm, 1.32±0.02 vs. 1.20±0.04, P=0.021), greater axon diameter (in µm, 0.92±0.01 vs. 0.89±0.03, P=0.035) and lower g-ratio (0.69±0.01 vs. 0.74±0.01, P=0.033) in the apical region around the implants. It may be assumed that the treatment protocol with IIP+IL is the preferred method to allow optimized peri-implant re-innervation, but further functional measurements are still required.International Journal of Oral Science advance online publication, 12 September 2014; doi:10.1038/ijos.2014.53.
- Microradiographic and histological evaluation of the bone-screw and bone-plate interface of orthodontic miniplates in patients. [JOURNAL ARTICLE]
- Eur J Orthod 2014 Sep 1.
Summary OBJECTIVES: To describe the tissue reactions at the bone-titanium interface of orthodontic miniplates in humans.Forty-two samples, consisting of tissue fragments attached or not to miniplates or their fixation screws, were collected from 24 orthodontic patients treated with miniplate anchorage, at the time of removal of their miniplates. The samples were embedded in methylmethacrylate and cut into undecalcified sections which were submitted to microradiographic analysis. The sections were also stained and examined under ordinary light.Three types of reactions were observed both on the histological sections and on the microradiographs. 1. The majority of the stable miniplates were easy to remove (34/42). The tissue samples collected consisted mainly in mature lamellar bone with some medullary spaces containing blood vessels, 2. two screws were highly osseointegrated and required the surgeon to remove them by trephining (2/42). They were surrounded by bone tissue which extended to the miniplate. The histological features were similar to the previous group, though the bone-screw contact was higher, and 3. in six samples obtained after unstable miniplate removal during the treatment, we observed either some woven bone trabeculae or loose connective tissue, without any histological sign of inflammation.For evident ethical reasons, our data were limited by the size of the tissue fragments and the limited number of patients and variety of clinical presentations. The healing reactions consisted mainly in mature lamellar bone tissue sparsely in contact with the screw or the miniplate, with signs of a moderate remodelling activity.