The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study.

BACKGROUND: Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. METHODS: Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. RESULTS: The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. CONCLUSIONS: Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.

Evaluation of graphene-derived bone scaffold exposure to the calvarial bone_in-vitro and in-vivo studies.

Graphene is a novel material which has recently been gaining great interest in the biomedical fields. Our previous study observed that graphene-derived particles help induce bone formation in a murine calvarial model. Here, we further developed a blended graphene-contained polycaprolactone (PCL/G) filament for application in a 3D-printed bone scaffold. Since implants are expected to be for long-term usage, in vitro cell culture and in vivo scaffold implants were evaluated in a critical-size bone defect calvarial model for over 60 weeks. Graphene greatly improved the mechanical strength by 30.2% compared to pure PCL. The fabricated PCL/G scaffolds also showed fine cell viability. In animal model, an abnormal electroencephalogram power spectrum and early signs of aging, such as hair graying and hair loss, were found in the group with a PCL/G scaffold compared to pure PCL scaffold. Neither of the abnormal symptoms caused death of all animals in both groups. The long-term use of graphene-derived biomaterials for in-vivo implants seems to be safe. But the comprehensive biosafety still needs further evaluation.

In vitro and in vivo Biological Responses to Graphene and Graphene Oxide: A Murine Calvarial Animal Study.

BACKGROUND: Graphene and its derivatives have recently gained popularity in the biomedical field. Previous studies have confirmed that both the mechanical strength and wear resistance of graphene-containing polyethylene have been greatly improved. Therefore, it is being considered as an alternative for artificial joint replacement liners. Based on the literature, the wear debris generated from the traditional polymers used for orthopedic liners could lead to particle-induced osteolysis and, consequently, failure of joint replacement. However, the biological response of this novel graphene-based polymer is still unclear. Therefore, the current study aimed to investigate the in vitro and in vivo biological effects of graphene and graphene oxide (GO) particles on bone. MATERIALS AND METHODS: The biological responses of graphene and GO particles were tested via in vitro and murine calvarial in vivo models. In the in vitro model, murine macrophage cells were mixed with particles and hydrogel and printed into two differently designed scaffolds; the induced proinflammatory cytokines were then tested. In the murine in vivo model, the particle size distribution was measured via SEM, and these particles were then administrated in the calvarial area, referring to our established model. A micro-CT and histological analysis were performed to examine the biological effects of the particles on bone health. The data were analyzed via the one-way analysis of variance to determine the differences between the groups. RESULTS: Both graphene and GO induced significantly higher TNF-α and IL-6 secretion compared with the control in the three-dimensional in vitro model. In the murine calvarial in vivo test, the graphene and GO particles increased the bone mass compared with the sham groups in the micro-CT analysis. Bone formation was also observed in the histological analysis. CONCLUSION: In these in vivo and in vitro studies, the graphene and GO wear debris did not seem to induce harmful biological response effect to bone. Bone formation around the skull was observed in the calvarial model instead. Graphene-containing biomaterials could be a suitable new material for application in orthopedic prostheses due to their benefit of eliminating the risk of particle-induce osteolysis.

First detection and molecular identification of Babesia vogeli from Rhipicephalus sanguineus (Acari: Ixodidae) in Taiwan.

A total of 578 Rhipicephalus sanguineus ticks collected from dogs in Taiwan were examined for Babesia by species-specific polymerase chain reaction assay based on the 18S small subunit ribosomal RNA (ssrRNA) gene. Babesia DNA was detected in 1.04 % (6/578) of Rh. sanguineus ticks. Phylogenetic analysis revealed that these Babesia spp. were genetically linked to the same clade within the genospecies of Babesia vogeli and could be discriminated from other genospecies of Babesia. Intra-species analysis based on the genetic distance values indicated a lower level (0.079) compared with other genospecies of Babesia (GD > 0.094) and out-group protozoa (GD > 0.236). This study provides the first molecular evidence of B. vogeli detected and identified in various stages of Rh. sanguineus ticks removed from dogs in Taiwan. Detection of Rh. sanguineus in flat male ticks may imply the possible mechanism of transstadial transmission in Rh. sanguineus ticks. The vector competence and the diversity of Babesia species harbored by Rh. sanguineus ticks need to be further investigated.

In vivo biological response to highly cross-linked and vitamin e-doped polyethylene--a particle-Induced osteolysis animal study.

Polyethylene particle-induced osteolysis is the primary limitation in the long-term success of total joint replacement with conventional ultra high molecular weight polyethylene (UHMWPE). Highly cross-linked polyethylene (HXLPE) and vitamin E-doped cross-linked polyethylene (VE-HXLPE) have been developed to increase the wear resistance of joint surfaces. However, very few studies have reported on the incidence of particle-induced osteolysis for these novel materials. The aim of this study was to use a particle-induced osteolysis animal model to compare the in vivo biological response to different polymer particles. Three commercially available polymers (UHMWPE, HXLPE, and VE-HXLPE) were compared. Osseous properties including the bone volume relative to the tissue volume (BV/TV), trabecular thickness (Tb. Th), and bone mineral density (BMD) were examined using micro computed tomography. Histological analysis was used to observe tissue inflammation in each group. This study demonstrated that the osseous properties and noticeable inflammatory reactions were obviously decreased in the HXLPE group. When compared with the sham group, a decrease of 12.7% was found in BV/TV, 9.6% in BMD and 8.3% in Tb.Th for the HXLPE group. The heightened inflammatory response in the HXLPE group could be due to its smaller size and greater amount of implanted particles. Vitamin E diffused in vivo may not affect the inflammatory and osteolytic responses in this model. The morphological size and total cumulative amount of implanted particles could be critical factors in determining the biological response.

The potential role of strontium ranelate in treating particle-induced osteolysis.

Ultra high molecular weight polyethylene (UHMWPE) wear-particle-induced osteolysis is one of the major issues affecting the long-term survival of total joint prostheses. Currently, there are no effective therapeutic options to prevent osteolysis from occurring. The aim of this study was to evaluate the role of strontium ranelate (SR) in reducing the risk of particle-induced osteolysis. Forty-eight C57BL/6J ultra-high molecular weight polyethylene (UHMWPE) particle-induced murine calvarial osteolysis models were used. The mice were randomized into four groups as: sham (Group 1), UHMWPE particles (Group 2), and SR with UHMWPE particles (Group 3 and Group 4). Groups 1 to 3 were sacrificed at two weeks and group 4 was sacrificed at the fourth week. The skulls were then analyzed with a high-resolution micro-CT. Histological evaluation was then conducted and osteoclast numbers were analyzed for comparison. Based on the micro-CT, percentage bone volume and trabecular thickness were found to be significantly higher in Group 4 than in Group 2 (p<0.001). Osteoclast numbers in SR treated groups (Group 3 and Group 4) were reduced when compared to groups that did not receive SR treatment (Group 2). These results indicated that SR treatment helps to increase bone volume percentage and trabecular thickness and also suppresses osteoclast proliferation. It is suggested that oral SR treatment could serve as an alternative therapy for preventing particle-induced osteolysis.

Overexpression of WW domain-containing oxidoreductase WOX1 preferentially induces apoptosis in human glioblastoma cells harboring mutant p53.

PURPOSE: Human WWOX gene encoding WW domain-containing oxidoreductase, named WWOX, FOR, or WOX1, has been studied in various types of cancer cells and shown to be a tumor suppressor with pro-apoptotic properties. Mutation or gain-of-function of p53 in glioma cells is associated with resistance to radiation therapy and poor prognosis. In this study, we overexpressed WOX1 to examine the pro-apoptotic activity against human glioblastoma cells harboring mutant p53. METHODS: Overexpression of WOX1 in glioblastoma cell lines and apoptosis-related assays were performed. RESULTS: Our results showed that overexpressed WOX1 induced apoptosis of glioblastoma U373MG harboring mutant p53 by causing hypoploidy and DNA fragmentation. However, ectopic WOX1 had no effect with U87MG possessing wild type p53. Unlike temozolomide, WOX1 induced apoptosis of U373MG cells via a mitochondria-independent and caspase-3-independent pathway. CONCLUSIONS: Overexpression of WOX1 preferentially inhibited viability and induced apoptosis in human glioblastoma cells expressing mutant p53 via a mechanism independent of the intrinsic apoptotic pathway. Conceivably, the survival of human glioblastoma cells depends upon interactions between the gain-of-function of p53 and WOX1. This suggests that modulation of WOX1 expression may be a novel strategy for treating human glioblastoma cells with mutant p53.