Treatment with resveratrol attenuates sublesional bone loss in spinal-cord-injured rats

Authors

Hua-Dong Wang, Ya-Min Shi, Li Li, Ji-Dong Guo, Yu-Peng Zhang, Shu-Xun Hou

Abstract

Background and purpose: Sublesional osteoporosis predisposes individuals with spinal cord injury (SCI) to an increased risk of low-trauma fracture. The aim of present work was to investigate the effect of treatment with resveratrol (RES) on sublesional bone loss in spinal-cord-injured rats. Experimental approach: Complete SCI was generated by surgical transaction of the cord at the T10-12 level. Treatment with RES (400 mg/kg body mass/day, intragastrically) was initiated 12 hours after the surgery for 10 days. Then, blood was collected and femurs and tibiae were removed for evaluation of the effects of RES on bone tissue after SCI. Key results: Treatment of SCI rats with RES prevented the reduction of bone mass including bone mineral content and bone mineral density in tibiae, preserved bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in tibiae, and preserved mechanical strength including ultimate load, stiffness, and energy in femurs. Treatment of SCI rats with RES enhanced femoral t-SH content, reduced femoral malondialdehyde and IL-6 mRNA levels. Treatment of SCI rats with RES suppressed the upregulation of mRNA levels of PPARγ, aP2, and LPL, and restored mRNA levels of Wnt1, Lrp5, Axin2, ctnnb1, IGF-1 and IGF-1R in femurs and tibiae. Conclusions and Implications: Treatment with RES attenuated sublesional bone loss in spinal-cord-injured rats, associated with abating oxidative stress, attenuating inflammation, depressing PPARγ signaling, and restoring Wnt/β-catenin and IGF-1 signaling.

Link to Article

http://dx.doi.org/10.1111/bph.12301

The Effects of Loading on the Preload and Dimensions of the Abutment Screw for a 3-Unit Cantilever-Fixed Prosthesis Design

Authors

Setia, Gaurav DDS, Yousef, Hoda DMD, MS, Ehrenberg, David DDS, MS, Luke, Allyn BA, BSCE, MSCE, Weiner, Saul DDS

Abstract

Objective: The purpose of this study was to use an in vitro model system to compare the effects on the screw torque and screw dimensions within 2 commercially available implant systems from occlusal loading on a cantilevered-fixed partial denture. Materials and Methods: Cantilevered implant-supported 3-unit prostheses with 2 premolar abutments and 1 premolar pontic (7.3 mm in length) were made on resin casts containing 2 implant analogs for 2 implant systems: BioLok Silhouette Tapered Implant System (Birmingham, AL) and Zimmer Tapered Screw-Vent Implant System (Carlsbad, CA) with 10 samples in each group. Each sample was loaded with either of 2 protocols: (1) a load of 50 N on the cantilevered pontic unit and (2) a loading of 150 N on all 3 units. The outcome measures were (1) changes in residual torque of the abutment screws and (2) changes in screw dimension. Results: The BioLok Silhouette Tapered Implant group demonstrated slight but statistically significant torque loss 18.8% to 28.5% in both abutment screws for both protocols, P <= 0.05, without any changes in screw dimension. In the Zimmer Tapered Screw-Vent Implant group, there was a significant elongation of the abutment screws and a markedly significant 44.4%, (P <= 0.01) loss in torque in the mesial screw and a 28.5%, (P <= 0.05) loss in torque in the distal screw when the cantilever alone was loaded. Conclusions: Differences in screw design influence the maintenance of preload and distortion of the shank. The influence of the interface design, namely an internal hex of 1 mm versus an external hex did not influence the preload. Cantilevered prostheses can cause loss of torque and dimensional changes in abutment screws.

Link to Article

http://dx.doi.org/10.1097/ID.0b013e31829c227a

Matrix generation within a macroporous non-degradable implant for osteochondral defects is not enhanced with partial...

Title

Matrix generation within a macroporous non-degradable implant for osteochondral defects is not enhanced with partial enzymatic digestion of the surrounding tissue: evaluation in an in vivo rabbit model

Authors

Aaron J. Krych, Florian Wanivenhaus, Kenneth W. Ng, Stephen Doty, Russell F. Warren, Suzanne A. Maher

Abstract

Articular cartilage defects are a significant source of pain, have limited ability to heal, and can lead to the development of osteoarthritis. However, a surgical solution is not available. To tackle this clinical problem, non-degradable implants capable of carrying mechanical load immediately after implantation and for the duration of implantation, while integrating with the host tissue, may be viable option. But integration between articular cartilage and non-degradable implants is not well studied. Our objective was to assess the in vivo performance of a novel macroporous, nondegradable, polyvinyl alcohol construct. We hypothesized that matrix generation within the implant would be enhanced with partial digestion of the edges of articular cartilage. Our hypothesis was tested by randomizing an osteochondral defect created in the trochlea of 14 New Zealand white rabbits to treatment with: (i) collagenase or (ii) saline, prior to insertion of the implant. At 1 and 3-month post-operatively, the gross morphology and histologic appearance of the implants and the surrounding tissue were assessed. At 3 months, the mechanical properties of the implant were also quantified. Overall, the hydrogel implants performed favorably; at all time-points and in all groups the implants remained well fixed, did not cause inflammation or synovitis, and did not cause extensive damage to the opposing articular cartilage. Regardless of treatment with saline or collagenase, at 1 month post-operatively implants from both groups had a contiguous interface with adjacent cartilage and were populated with chondrocyte-like cells. At 3 months fibrous encapsulation of all implants was evident, there was no difference between area of aggrecan staining in the collagenase versus saline groups, and implant modulus was similar in both groups; leading us to reject our hypothesis. In summary, a porous PVA osteochondral implant remained well fixed in a short term in vivo osteochondral defect model; however, matrix generation within the implant was not enhanced with partial digestion of adjacent articular cartilage.

Link to Article

http://dx.doi.org/10.1007/s10856-013-4999-x

Bmp2 gene in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

Authors

W. Yang, D. Guo, M.A. Harris, Y. Cui, J. Gluhak-Heinrich, J. Wu, X.-D. Chen, C Skinner, J. Nyman, J.R. Edwards, G.R. Mundy, A. Lichtler, B. Kream, D. Rowe, I. Kalajzic, V. David, D. Quarles, D. Villareal, Greg Scott, Manas Ray, S. Liu, J.F. Martin, Y. Mishina and S.E. Harris

Abstract

We generated a new Bmp2 conditional knock-out allele without a neo cassette and removed Bmp2 gene in osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in reduced bone formation rate, and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSC), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Several marker genes of MSC (α-SMA, CD146 and Angiopoietin-1), in vitro CFU assays and deletion of the Bmp2 gene in vitro in α-SMA+ BMSC support our conclusions. Critical roles of the Bmp2 gene in osteoblasts and MSC are a vital link between bone formation, vascularization and mesenchymal stem cells.

Link to Article

http://dx.doi.org/10.1242/cs.118596

Erosive Arthritis and Hepatic Granuloma Formation Induced by Peptidoglycan Polysaccharide in Rats Is Aggravated by Prasugrel Treatment

Authors

Analia E. Garcia, Mario C. Rico, Elisabetta Liverani, Raul A. DeLa Cadena, Paul F. Bray, Satya P. Kunapuli

Abstract

Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS) in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with untreated arthritic rats, in terms of augmented macroscopic joint diameter associated with significant signs of inflammation, histomorphometric measurements of the hind joints and elevated platelet number. Moreover, fibrosis at the pannus, assessed by immunofluorescence of connective tissue growth factor, was increased in arthritic rats treated with prasugrel. In addition to the arthritic manifestations, hepatomegaly, liver granulomas and giant cell formation were observed after PG-PS induction and even more after prasugrel exposure. Cytokine plasma levels of IL-1 beta, IL-6, MIP1 alpha, MCP1, IL-17 and RANTES were increased in arthritis-induced animals. IL-10 plasma levels were significantly decreased in animals treated with prasugrel. Overall, prasugrel enhances inflammation in joints and liver of this animal model. Since prasugrel metabolites inhibit neutrophil function ex-vivo and the effects of both clopidogrel and prasugrel metabolites on platelets are identical, we conclude that the thienopyridines metabolites might exert non-platelet effects on other immune cells to aggravate inflammation.

Link to Article

http://dx.doi.org/10.1371/journal.pone.0069093

The Interleukin 8 Expression and its Possible Relationship with Degenerated and Injured Human Intervertebral Discs

Authors

Basit Saleem Qazi, Tang Kai and Asma Saleem Qazi

Abstract

Purpose: Cervical and Lumbar degenerative disc diseases (DDD) are a common disease of advanced age characterized by progressive changes in the intervertebral disc and associated structures. There have been great efforts for years to explain its pathophysiological mechanism(s). This study aims to provide the expression of IL-8 in a population of patients with lumbar disc herniation, cervical stenosis and vertebral fracture. Material and methods: We compared the level of IL-8 expression in the non-degenerated and degenerated intervertebral disc samples obtained from patients who underwent surgery for vertebral fracture (non degenerated disc), lumbar disc herniation and cervical stenosis (degenerated disc), whose clinical and radiological features were suggestive of disc degeneration. IL-8 expression was studied by using the western blot, immunohistochemistry and enzyme linked immune absorbent assay methods. This study includes comparison of IL-8 concentration in groups based on patient’s age and diagnosis. Results: Significantly higher levels of IL-8 expressions were found in patient with advance age, more in vertebral fracture as compared to lumbar disc herniation and cervical stenosis patients. Conclusion: The findings suggest that both local inflammatory responses occur in lumbar disc herniation, cervical stenosis and vertebral fracture patients. Using specific cytokines either by local or systemic application may reverse the degenerative process.

Link to Article

http://dx.doi.org/10.4172/2165-7939.1000135