Particle-induced bone loss by osteoclasts is a common cause of aseptic loosening around implants. This study investigates whether caffeic acid phenethyl ester (CAPE), a potent and specific inhibitor of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 and nuclear factor kappa B, at a low dose reduces bone resorption in a murine calvarial model of polyethylene (PE) particle-induced osteolysis. The effects of particles and CAPE treatment on gastrointestinal tract (GIT) histopathology were also evaluated. Mice were scanned using in vivo animal micro-computed tomography (μCT) as a baseline measurement. PE particles (2.82 × 10(9) particles/mL) were implanted over the calvariae on day 0. CAPE was administered subcutaneously (1 mg/kg/day) at days 0, 4, 7 and 10. Mice were killed at day 14 and serum was analysed for Type-1 carboxyterminal collagen crosslinks (CTX)-1 and osteoclast-associated receptor (OSCAR) levels. Ex vivo μCT scans were conducted to assess bone volume (BV) change and percentage area of calvarial surface resorbed. Calvarial and GIT tissue was processed for histopathology. By day 14, PE particles significantly induced calvarial bone loss compared with control animals as evidenced by resorption areas adjacent to the implanted PE in three-dimensional μCT images, an increase in percentage of resorbed area (p = 0.0022), reduction in BV (p = 0.0012) and increased Tartrate-resistant acid phosphatase positive cells. Serum CTX-1 (p = 0.0495) and OSCAR levels (p = 0.0006) significantly increased in the PE implant group. CAPE significantly inhibited PE particle-induced calvarial osteolysis, as evidenced by a significant reduction in surface bone resorption (p = 0.0012) and volumetric change (p = 0.0154) compared with PE only, but had no effect on systemic CTX-1. Neither particles nor CAPE had an effect on GIT histopathology.
The study aimed to determine the effects of parthenolide (PAR) on bone volume (BV) and bone surface resorption as assessed by live-animal microcomputed tomography (μCT) and possible osteocyte death as indicated by empty lacunae histologically in polyethylene (PE) particle-induced calvarial osteolysis in mice. Baseline μCT scans were conducted 7 days preimplantation of 2 × 10(8) PE particles/mL over the calvariae (day 0). PAR at 1 mg/kg/day was subcutaneously injected on days 0, 4, 7, and 10. At day 14, BV and surface resorption was analyzed with μCT. Calvarial tissue was processed for histomorphometric osteocyte evaluation. Serum was analyzed for type-1 carboxy-terminal collagen crosslinks (CTX-1) and osteoclast associated receptor (OSCAR) levels by ELISA. PE significantly decreased BV (p = 0.0368), increased surface bone resorption area (p = 0.0022), and increased the percentage of empty lacunae (p = 0.0043). Interestingly, PAR significantly reduced the resorption surface area (p = 0.0022) and the percentage of empty osteocyte lacunae (p = 0.0087) in the PE-calvariae, but it did not affect BV, serum CTX-1 or OSCAR levels. The ability of PAR to inhibit PE-induced surface bone erosion may better reflect the in vivo situation, where bone resorption occurs on the surface at the bone-implant interface and may also be related to the role of osteocytes in this pathology.
21 (3), 699-705 2006). This soft tissue neoplasm has gained an interest due to its diversity of histologic appearances, overlapping pattern, the rarity of the tumour, and the need of supportive and confirmatory tests which often renders MPNST as diagnostically challenging neoplasm. All these may justify to the delay in diagnosis. MPNST is rare, aggressive soft tissue sarcomas associated with poor prognosis. The diagnosis of MPNST relies on morphology and IHC interpretation. Differentiating MPNST from other types of spindle cell neoplasm is important for prognosis and management. Several markers have been suggested to distinguish MPNST from other soft tissue
Changes in mitochondrial bioenergetics are believed to take place during osteoclastogenesis. This study aims to assess changes in mitochondrial bioenergetics and reactive oxygen species (ROS) levels during polyethylene (PE)-induced osteoclastogenesis in vitro. For this purpose, RAW264.7 cells were cultured for nine days and allowed to differentiate into osteoclasts in the presence of PE and RANKL. The total TRAP-positive cells, resorption activity, expression of osteoclast marker genes, ROS level, mitochondrial bioenergetics, glycolysis, and substrate utilization were measured. The effect of tocotrienols-rich fraction (TRF) treatment (50 ng/mL) on those parameters during PE-induced osteoclastogenesis was also studied. During PE-induced osteoclastogenesis, as depicted by an increase in TRAP-positive cells and gene expression of osteoclast-related markers, higher proton leak, higher extracellular acidification rate (ECAR), as well as higher levels of ROS and NADPH oxidases (NOXs) were observed in the differentiated cells. The oxidation level of some substrates in the differentiated group was higher than in other groups. TRF treatment significantly reduced the number of TRAP-positive osteoclasts, bone resorption activity, and ROS levels, as well as modulating the gene expression of antioxidant-related genes and mitochondrial function. In conclusion, changes in mitochondrial bioenergetics and substrate utilization were observed during PE-induced osteoclastogenesis, while TRF treatment modulated these changes.
Background:The receptor activator of nuclear factor kappa B ligand (RANKL) is one of the key regulators of bone remodelling in bone oncology, including osteosarcoma. We assessed RANKL immunohistochemical expression in osteosarcoma, its association, and disease-free survival with the patients' clinicopathological characteristics. Methods: One hundred osteosarcoma cases from 2003 to 2018 in Hospital Universiti Sains Malaysia were retrieved. The tissue samples were stained for RANKL, and the association with the clinicopathological characteristics was evaluated. Staining was interpreted in a semiquantitative scoring system and classified into negative and positive expressions. Results: Eighty-two cases had a positive expression of RANKL in which 56 and 26 patients were classified as low expression and high expression, respectively. The positive expression of RANKL did not show a significant association with clinicopathological characteristics. However, Kaplan Meier survival analysis showed a significant improvement in the disease-free survival patients who underwent limb salvage surgery (LSS) than amputated patients (p-value 0.002), whereas poorer survival was observed among conventional osteosarcomas compared to non-conventional osteosarcoma (p-value 0.01). Conclusion: Limb salvage surgery had proven to improve osteosarcoma patients' survival compared to amputation, which could improve overall quality of life in osteosarcoma patients. However, our data did not show a significant association between positive RANKL immunohistochemistry with any of the clinicopathological characteristics and patients' final survival. Further studies may be acquired to understand the suitability of using RANKL immunohistochemistry as prognostication in the management of osteosarcoma patients.
The field of bone tissue engineering has shown a great variety of bone graft substitute materials under development to date, with the aim to reconstruct new bone tissue while maintaining characteristics close to the native bone. Currently, insufficient scaffold degradation remains the critical limitation for the success of tailoring the bone formation turnover rate. This study examines novel scaffold formulations to improve the degradation rate in vivo, utilising chitosan (CS), hydroxyapatite (HAp) and fluorapatite (FAp) at different ratios. Previously, the P28 peptide was reported to present similar, if not better performance in new bone production to its native protein, bone morphogenetic protein-2 (BMP-2), in promoting osteogenesis in vivo. Therefore, various P28 concentrations were incorporated into the CS/HAp/FAp scaffolds for implantation in vivo. H&E staining shows minimal scaffold traces in most of the defects induced after eight weeks, showing the enhanced biodegradability of the scaffolds in vivo. The HE stain highlighted the thickened periosteum indicating a new bone formation in the scaffolds, where CS/HAp/FAp/P28 75 µg and CS/HAp/FAp/P28 150 µg showed the cortical and trabecular thickening. CS/HAp/FAp 1:1 P28 150 µg scaffolds showed a higher intensity of calcein green label with the absence of xylenol orange label, which indicates that mineralisation and remodelling was not ongoing four days prior to sacrifice. Conversely, double labelling was observed in the CS/HAp/FAp 1:1 P28 25 µg and CS/HAp/FAp/P28 75 µg, which indicates continued mineralisation at days ten and four prior to sacrifice. Based on the HE and fluorochrome label, CS/HAp/FAp 1:1 with P28 peptides presented a consistent positive osteoinduction following the implantation in the femoral condyle defects. These results show the ability of this tailored formulation to improve the scaffold degradation for bone regeneration and present a cost-effective alternative to BMP-2.
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