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woven bone [keywords]
- Runx2-Smad signaling impacts the progression of tumor-induced bone disease. [JOURNAL ARTICLE]
- Int J Cancer 2014 Jul 23.
Runx2, a master regulator of osteogenesis, is abnormally expressed in advanced prostate cancer. Here we addressed Runx2 contribution to formation of prostate cancer-related osteolytic and osteoblastic bone lesions by mediating TGFβ/BMP signaling through direct interaction with Smads. Further, we examined involvement of the Runx2-Smad complex in mediating tumor growth and distal metastasis. To identify Runx2-Smad specific mechanisms of prostate tumor activity in bone, we generated PC3 prostate cancer cell lines expressing Runx2-WT or one of two mutant proteins (Runx2-HTY and Runx2-ΔC) that each disrupt the Runx2-Smad interaction, either directly through a point mutation or by deletion of the functional C-terminus, respectively. Intratibial tumors generated from these cells revealed that Runx2-WT expressing cells resulted in predominantly osteolytic disease, while cells expressing mutant proteins exhibited tumors with mixed osteolytic/osteoblastic lesions. Extent of bone loss and of woven bone formation was assessed by radiography and micro-computed tomography. Bioluminescent imaging showed the presence of labeled prostate cancer cells in the lung at the latest time point examined, with Runx2-WT group exhibiting increased incidence of tumor cells in lung. Notably, disruption of the Runx2-Smad interaction significantly reduced incidence and size of lung tumors. Altered expression of Runx2 target genes involved in invasion, growth, adhesion and metastasis supported our findings. Thus, our studies demonstrate that Runx2 in prostate cancer cells plays a significant role in intratibial prostate cancer-related tumor growth and bone loss through mechanisms mediated by the Runx2-Smad signaling pathway. This work expands upon the potential importance of Runx2 as a therapeutic target in cancer. © 2014 Wiley Periodicals, Inc.
- The effect of implant diameter on osseointegration utilizing simplified drilling protocols. [JOURNAL ARTICLE]
- Clin Oral Implants Res 2013 Oct 8.
To observe and to compare histologically and histomorphometrically, the combined effect of drilling sequence and implant diameter in vivo.A total of 72 alumina-blasted and acid-etched Ti-6Al-4V implants with three different diameters (3.75, 4.2, and 5 mm, n = 24 for each group) were placed in the right and left tibiae of 12 beagle dogs. Within the same diameter group, half of the implants were inserted after a simplified drilling procedure (pilot drill + final diameter drill) on one tibia and the other half were placed using the conventional drilling procedure on the other tibia. After 1 week, half of the animals (n = 6) were sacrificed, and the other half was sacrificed after 5 weeks (n = 6). The retrieved bone-implant samples were subjected to non-decalcified histologic sectioning, and the bone-to-implant contact (BIC) and the bone area fraction occupancy (BAFO) were analyzed. Primary statistical analysis used a mixed model analysis of variance with significance level set at P < 0.05.Histologic observation showed that at 1 week, immature woven bone formed in vicinity of the implant, whereas at 5 weeks, the woven bone was replaced by lamellar bone, which formed in proximity with the implant. Histomorphometrically, the simplified technique was associated with significantly greater BIC and BAFO after 1 week. Differences between techniques were not longer apparent after 5 weeks, but BAFO was inversely and significantly associated with implant diameter at that time.The simplified technique did not impair either early or late bone formation for any tested implant diameter; however, wider diameters were associated with less bone formation at longer healing times for both techniques.
- A large multifocal aggressive osteoblastoma of mandible: an immunohistochemistry case study report. [Journal Article]
- J Dent Res Dent Clin Dent Prospects 2014; 8(1):51-5.
Aggressive osteoblastoma (AO) is a benign osteoblastic tumor which is rare in the head and neck region. Clinical and histo-logical features are therefore overlap with other benign and low-grade malignant tumors. The aim of this article is to report and discuss the differential diagnosis of an aggressive osteoblastoma in the mandible. A 25-year-old male patient reported with pain and asymmetry on the left side of the face since 8 months previously. Radiographic evaluation showed a mixed lesion extending from approximately the lower left premolar to the third molar region. After incisional biopsy, resection with continuity defect was carried out. Microscopic findings showed woven bone and bony trabeculae with varied degrees of mineralization along with sheets of osteoblast cells. Immunohistochemistry showed that p53 and cytokeratin (CK) were negative and ki-67 index was 7%. Postoperative follow-up for 15 months showed no evidence of recurrence.
- BDNF and its TrkB receptor in human fracture healing. [JOURNAL ARTICLE]
- Ann Anat 2014 Jun 16.
Fracture healing is a physiological process of repair which proceeds in stages, each characterized by a different predominant tissue in the fracture gap. Matrix reorganization is regulated by cytokines and growth factors. Neurotrophins and their receptors might be of importance to osteoblasts and endothelial cells during fracture healing. The aim of this study was to examine the presence of brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B receptor (TrkB) during human fracture healing. BDNF and TrkB were investigated in samples from human fracture gaps and cultured cells using RT-PCR, Western blot, and immunohistochemistry. Endothelial cells and osteoblastic cell lines demonstrated a cytoplasmic staining pattern of BDNF and TrkB in vitro. At the mRNA level, BDNF and TrkB were expressed in the initial and osteoid formation phase of human fracture healing. In the granulation tissue of fracture gap, both proteins - BDNF and TrkB - are concentrated in endothelial and osteoblastic cells at the margins of woven bone suggesting their involvement in the formation of new vessels. There was no evidence of BDNF or TrkB during fracture healing in chondrocytes of human enchondral tissue. Furthermore, BDNF is absent in mature bone. Taken together, BDNF and TrkB are involved in vessel formation and osteogenic processes during human fracture healing. The detection of BDNF and its TrkB receptor during various stages of the bone formation process in human fracture gap tissue were shown for the first time. The current study reveals that both proteins are up-regulated in human osteoblasts and endothelial cells in fracture healing.
- Citrate Crosslinked Gels with Strain Reversibility and Viscoelastic Behavior Accelerates Healing of Osteochondral Defects in Rabbit Model. [JOURNAL ARTICLE]
- Langmuir 2014 Jun 27.
Most living tissues are viscoelastic in nature. Self-repair due to dissipation of energy by reversible bonds prevents rupture of molecular backbone in these tissues. Recent studies therefore, aim to synthesize biomaterials that approximate mechanical performance of biological materials with self-recovery property. We report an environmentally friendly method for development of ionotropically crosslinked viscoelastic chitosan gels with modulus comparable to living tissues. The strain recovery property was found to be highest for the gels with lowest crosslinking density. Force-displacement curve showed significant hysteresis due to presence of reversible bonds in the crosslinked gels. Nanoindentation studies demonstrated creep phenomenon for the crosslinked chitosan gels. Creep, hysteresis and plasticity index confirmed viscoelastic behavior of the crosslinked gels. The viscoelastic gels were implanted at osteochondral defect sites to assess tissue regeneration ability. In vivo results demonstrated early cartilage formation and woven bone deposition for defects filled with the gels compared to non-treated defects.
- Quantification of intraskeletal histovariability in Alligator mississippiensis and implications for vertebrate osteohistology. [Journal Article]
- PeerJ 2014.:e422.
Bone microanalyses of extant vertebrates provide a necessary framework from which to form hypotheses regarding the growth and skeletochronology of extinct taxa. Here, we describe the bone microstructure and quantify the histovariability of appendicular elements and osteoderms from three juvenile American alligators (Alligator mississippiensis) to assess growth mark and tissue organization within and amongst individuals, with the intention of validating paleohistological interpretations. Results confirm previous observations that lamellar and parallel fibered tissue organization are typical of crocodylians, and also that crocodylians are capable of forming woven tissue for brief periods. Tissue organization and growth mark count varies across individual skeletal elements and reveal that the femur, tibia, and humerus had the highest annual apposition rates in each individual. Cyclical growth mark count also varies intraskeletally, but data suggest these inconsistencies are due to differing medullary cavity expansion rates. There was no appreciable difference in either diaphyseal circumference or cyclical growth mark circumferences between left and right element pairs from an individual if diaphyses were sampled from roughly the same location. The considerable intraskeletal data obtained here provide validation for long-held paleohistology assumptions, but because medullary expansion, cyclical growth mark formation, and variable intraskeletal growth rates are skeletal features found in tetrapod taxa living or extinct, the validations presented herein should be considered during any tetrapod bone microanalysis.
- Central Giant Cell Granuloma in Pediatric Maxilla: Surgical Management. [JOURNAL ARTICLE]
- J Craniofac Surg 2014 Jun 18.
Central giant cell granuloma (CGCG) is an intraosseous lesion consisting of fibrous cellular tissue that contains multiple foci of hemorrhage, multinucleated giant cells, and occasional trabeculae of woven bone. An 8-year-old boy presented himself complaining of a painless swelling in the left maxilla that had started 1 year. Computed tomography (CT) scan confirmed a poorly defined multilocular radiolucent lesion in the left maxilla crossing the midline. The patient underwent enucleation through an intraoral approach of the lesion. The biopsy revealed multinucleated giant cells in a fibrous stroma. A CT was taken approximately 1 year postoperatively. There was no clinical or radiographic evidence of recurrence. Therefore, surgical treatment of CGCG can be performed, trying to preserve the surrounding anatomic structures, which can be maintained in case the lesion does not show an aggressive clinical behavior, avoiding large surgical defects which are undesirable in children.
- Topical Simvastatin Improves the Pro-Angiogenic and Pro-Osteogenic Properties of Bioglass Putty in the Rat Calvaria Critical-Size Model. [JOURNAL ARTICLE]
- J Oral Implantol 2014 Jun; 40(3):251-258.
Objective was to describe the effect of bioactive glass putty with and without topical simvastatin on new bone formation in critical-sized defects of rat calvaria. A calvarial bone defect was created in 20 male Wistar rats and filled with bioactive glass alone (n = 10) or combined with simvastatin (n = 10). After 4 weeks, the defects were histomorphometrically evaluated for volume fraction (Vv) of woven bone, vessel density, bioglass quantity, and inflammation. Compared to the bioglass-only group, rats treated with simvastatin had greater Vv of blood vessels (3.3% ± 0.7 vs 1.6% ± 0.1, P = .0002) and new bone (2.3% ± 0.2 vs 1.8% ± 2.5, P = .003). The Vv of the bioglass remnants in the bioglass-only group was higher than in the group treated with simvastatin (2.4% ± 0.08 vs 1.7% ± 0.3, P < .0004). Chronic inflammation was noted in 1 rat from each group. Topical simvastatin seems to improve the pro-angiogenic and pro-osteogenic properties of bioglass putty in rat calvaria critical-size defects without significant inflammation.
- Delayed Fracture Healing and Increased Callus Adiposity in a C57BL/6J Murine Model of Obesity-Associated Type 2 Diabetes Mellitus. [JOURNAL ARTICLE]
- PLoS One 2014; 9(6):e99656.
Impaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture healing in type 1 DM (T1DM) has been studied using animal models, an investigation into delayed healing in an animal model of T2DM has not yet been performed.Male C57BL/6J mice at 5 weeks of age were placed on either a control lean diet or an experimental high-fat diet (HFD) for 12 weeks. A mid-diaphyseal open tibia fracture was induced at 17 weeks of age and a spinal needle was used for intra-medullary fixation. Mice were sacrificed at days 7, 10, 14, 21, 28, and 35 for micro-computed tomography (μCT), histology-based histomorphometry and molecular analyses, and biomechanical testing.HFD-fed mice displayed increased body weight and impaired glucose tolerance, both characteristic of T2DM. Compared to control mice, HFD-fed mice with tibia fractures showed significantly (p<0.001) decreased woven bone at day 28 by histomorphometry and significantly (p<0.01) decreased callus bone volume at day 21 by μCT. Interestingly, fracture calluses contained markedly increased adiposity in HFD-fed mice at days 21, 28, and 35. HFD-fed mice also showed increased PPARγ immunohistochemical staining at day 14. Finally, calluses from HFD-fed mice at day 35 showed significantly (p<0.01) reduced torsional rigidity compared to controls.Our murine model of T2DM demonstrated delayed fracture healing and weakened biomechanical properties, and was distinctly characterized by increased callus adiposity. This suggests altered mesenchymal stem cell fate determination with a shift to the adipocyte lineage at the expense of the osteoblast lineage. The up-regulation of PPARγ in fracture calluses of HFD-fed mice is likely involved in the proposed fate switching.
- Wound healing of osteotomy defects prepared with piezo or conventional surgical instruments: a pilot study in rabbits. [JOURNAL ARTICLE]
- J Investig Clin Dent 2014 May 22.
The aim of the present study was to evaluate and compare the wound-healing process following osteotomies performed with either conventional rotary burs or piezoelectric surgery in a rabbit model.Two types of osteotomy window defects of the nasal cavities were prepared on the nasal bone of 16 adult New Zealand white rabbits with either a conventional rotary bur or piezo surgery. The defects were covered with a resorbable membrane. Four animals were killed at 1, 2, 3, and 5 weeks after the surgical procedure, respectively. Histological and morphometric evaluations were performed to assess the volumetric density of various tissue components: the blood clot, vascularized structures, provisional matrix, osteoid, mineralized bone, bone debris, residual tissue, and old bone.Significantly more bone debris was found at 1( ) week in the conventionally-prepared defects compared to the piezo surgically-prepared defects. At 2 and 3 weeks, a newly-formed hard tissue bridge, mainly composed of woven bone, was seen; however, no statistically-significant differences were observed. At 5 weeks, the defects were completely filled with newly-formed bone.The defects prepared by piezo surgery showed a significantly decreased proportion of bone debris at 1 week, compared to conventional rotary bur defect.