Association between postmenopausal osteoporosis and experimental periodontitis

To investigate the correlation between postmenopausal osteoporosis (PMO) and the pathogenesis of periodontitis, ovariectomized rats were generated and the experimental periodontitis was induced using a silk ligature. The inflammatory factors and bone metabolic markers were measured in the serum and periodontal tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme-linked immunosorbent assays, and immunohistochemistry. The bone mineral density of whole body, pelvis, and spine was analyzed using dual-energy X-ray absorptiometry and image analysis. All data were analyzed using SPSS 13.0 statistical software. It was found that ovariectomy could upregulate the expression of interleukin- (IL-)6, the receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10 expression in periodontal tissues, which resulted in progressive alveolar bone loss in experimental periodontitis. This study indicates that changes of cytokines and bone turnover markers in the periodontal tissues of ovariectomized rats contribute to the damage of periodontal tissues.

Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate

The osteoimmunomodulatory property of bone biomaterials is a vital property determining the in vivo fate of the implants. Endowing bone biomaterials with favorable osteoimmunomodulatory properties is of great importance in triggering desired immune response and thus supports the bone healing process. Magnesium (Mg) has been recognized as a revolutionary metal for applications in orthopedics due to it being biodegradable, biocompatible, and having osteoconductive properties. However, Mg's high rate of degradation leads to an excessive inflammatory response and this has restricted its application in bone tissue engineering. In this study, β-tricalcium phosphate (β-TCP) was used to coat Mg scaffolds in an effort to modulate the detrimental osteoimmunomodulatory properties of Mg scaffolds, due to the reported favorable osteoimmunomodulatory properties of β-TCP. It was noted that macrophages switched to the M2 extreme phenotype in response to the Mg-β-TCP scaffolds, which could be due to the inhibition of the toll like receptor (TLR) signaling pathway. VEGF and BMP2 were significantly upregulated in the macrophages exposed to Mg-β-TCP scaffolds, indicating pro-osteogenic properties of macrophages in β-TCP modified Mg scaffolds. This was further demonstrated by the macrophage-mediated osteogenic differentiation of bone marrow stromal cells (BMSCs). When BMSCs were stimulated by conditioned medium from macrophages cultured on Mg-β-TCP scaffolds, osteogenic differentiation of BMSCs was significantly enhanced; whereas osteoclastogenesis was inhibited, as indicated by the downregualtion of MCSF, TRAP and inhibition of the RANKL/RANK system. These findings suggest that β-TCP coating of Mg scaffolds can modulate the scaffold's osteoimmunomodulatory properties, shift the immune microenvironment towards one that favors osteogenesis over osteoclastogenesis. Endowing bone biomaterials with favorable osteoimmunomodulatory properties can be a highly valuable strategy for the development or modification of advanced bone biomaterials.

Nutrient element-based bioceramic coatings on titanium alloy stimulating osteogenesis by inducing beneficial osteoimmmunomodulation

A paradigm shift has taken place in which bone implant materials has gone from being relatively inert to having immunomodulatory properties, indicating the importance of immune response when these materials interact with the host tissues. It has therefore become important to endow the implant materials with immunomodulatory properties favouring osteogenesis and osseointegration. Strontium, zinc and silicon are bioactive elements that have important roles in bone metabolism and that also elicit significant immune responses. In this study, Sr-, Zn- and Si-containing bioactive Sr2ZnSi2O7 (SZS) ceramic coatings on Ti–6Al–4V were successfully prepared by a plasma-spray coating method. The SZS coatings exhibited slow release of the bioactive ions with significantly higher bonding strength than hydroxyapatite (HA) coatings. SZS-coated Ti–6Al–4V elicited significant effects on the immune cells, inhibiting the release of pro-inflammatory cytokines and fibrosis-enhancing factors, while upregulating the expression of osteogenic factors of macrophages; moreover, it could also inhibit the osteoclastic activities. The RANKL/RANK pathway, which enhances osteoclastogenesis, was inhibited by the SZS coatings, whereas the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) was significantly enhanced by the SZS coatings/macrophages conditioned medium, probably via the activation of BMP2 pathway. SZS coatings are, therefore, a promising material for orthopaedic applications, and the strategy of manipulating the immune response by a combination of bioactive elements with controlled release has the potential to endow biomaterials with beneficial immunomodulatory properties.

β-Arrestin2 regulates RANKL and Ephrins gene expression in response to bone remodeling in mice

PTH-stimulated intracellular signaling is regulated by the cytoplasmic adaptor molecule barrestin. We reported that the response of cancellous bone to intermittent PTH is reduced in b-arrestin22/2 mice and suggested that b-arrestins could influence the bone mineral balance by controlling RANKL and osteoprotegerin (OPG) gene expression. Here, we study the role of b-arrestin2 on the in vitro development and activity of bone marrow (BM) osteoclasts (OCs) and Ephrins ligand (Efn), and receptor (Eph) mRNA levels in bone in response to PTH and the changes of bone microarchitecture in wildtype (WT) and barrestin2 2/2 mice in models of bone remodeling: a low calcium diet (LoCa) and ovariectomy (OVX). The number of PTH-stimulated OCs was higher in BM cultures from b-arrestin22/2 compared with WT, because of a higher RANKL/OPG mRNA and protein ratio, without directly influencing osteoclast activity. In vivo, high PTH levels induced by LoCa led to greater changes in TRACP5b levels in b-arrestin22/2 compared with WT. LoCa caused a loss of BMD and bone microarchitecture, which was most prominent in b-arrestin22/2. PTH downregulated Efn and Eph genes in b-arrestin22/2, but not WT. After OVX, vertebral trabecular bone volume fraction and trabecular number were lower in b-arrestin22/2 compared with WT. Histomorphometry showed that OC number was higher in OVX-b-arrestin22/2 compared with WT. These results indicate that b-arrestin2 inhibits osteoclastogenesis in vitro, which resulted in decreased bone resorption in vivo by regulating RANKL/OPG production and ephrins mRNAs. As such, b-arrestins should be considered an important mechanism for the control of bone remodeling in response to PTH and estrogen deprivation.

Genetic determinants of bone density and fracture risk: State of the art and future directions

Context: Osteoporosis is a common, highly heritable condition that causes substantial morbidity and mortality, the etiopathogenesis of which is poorly understood. Genetic studies are making increasingly rapid progress in identifying the genes involved. Evidence Acquisition and Synthesis: In this review, we will summarize the current understanding of the genetics of osteoporosis based on publications from PubMed from the year 1987 onward. Conclusions: Most genes involved in osteoporosis identified to date encode components of known pathways involved in bone synthesis or resorption, but as the field progresses, new pathways are being identified. Only a small proportion of the total genetic variation involved in osteoporosis has been identified, and new approaches will be required to identify most of the remaining genes.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Low rank Runge-Kutta methods, symplecticity and stochastic Hamiltonian problems with additive noise

In this paper we extend the ideas of Brugnano, Iavernaro and Trigiante in their development of HBVM($s,r$) methods to construct symplectic Runge-Kutta methods for all values of $s$ and $r$ with $s\geq r$. However, these methods do not see the dramatic performance improvement that HBVMs can attain. Nevertheless, in the case of additive stochastic Hamiltonian problems an extension of these ideas, which requires the simulation of an independent Wiener process at each stage of a Runge-Kutta method, leads to methods that have very favourable properties. These ideas are illustrated by some simple numerical tests for the modified midpoint rule.

An extension to the rank constraint for improving the reliability of stereo matching algorithms using the rank transform

The rank transform is one non-parametric transform which has been applied to the stereo matching problem The advantages of this transform include its invariance to radio metric distortion and its amenability to hardware implementation. This paper describes the derivation of the rank constraint for matching using the rank transform Previous work has shown that this constraint was capable of resolving ambiguous matches thereby improving match reliability A new matching algorithm incorporating this constraint was also proposed. This paper extends on this previous work by proposing a matching algorithm which uses a dimensional match surface in which the match score is computed for every possible template and match window combination. The principal advantage of this algorithm is that the use of the match surface enforces the left�right consistency and uniqueness constraints thus improving the algorithms ability to remove invalid matches Experimental results for a number of test stereo pairs show that the new algorithm is capable of identifying and removing a large number of in incorrect matches particularly in the case of occlusions

An accurate and reliable stereo matching algorithm incorporating the rank constraint

A fundamental problem faced by stereo vision algorithms is that of determining correspondences between two images which comprise a stereo pair. This paper presents work towards the development of a new matching algorithm, based on the rank transform. This algorithm makes use of both area-based and edge-based information, and is therefore referred to as a hybrid algorithm. In addition, this algorithm uses a number of matching constraints,including the novel rank constraint. Results obtained using a number of test pairs show that the matching algorithm is capable of removing a significant proportion of invalid matches. The accuracy of matching in the vicinity of edges is also improved.

A hybrid stereo matching algorithm incorporating the rank constraint

A fundamental problem faced by stereo vision algorithms is that of determining correspondences between two images which comprise a stereo pair. This paper presents work towards the development of a new matching algorithm, based on the rank transform. This algorithm makes use of both area-based and edge-based information, and is therefore referred to as a hybrid algorithm. In addition, this algorithm uses a number of matching constraints, including the novel rank constraint. Results obtained using a number of test pairs show that the matching algorithm is capable of removing most invalid matches. The accuracy of matching in the vicinity of edges is also improved.

A constraint to improve the reliability of stereo matching using the rank transform

The rank transform is a non-parametric technique which has been recently proposed for the stereo matching problem. The motivation behind its application to the matching problem is its invariance to certain types of image distortion and noise, as well as its amenability to real-time implementation. This paper derives an analytic expression for the process of matching using the rank transform, and then goes on to derive one constraint which must be satisfied for a correct match. This has been dubbed the rank order constraint or simply the rank constraint. Experimental work has shown that this constraint is capable of resolving ambiguous matches, thereby improving matching reliability. This constraint was incorporated into a new algorithm for matching using the rank transform. This modified algorithm resulted in an increased proportion of correct matches, for all test imagery used.

Estimating the probability of an invalid match for matching using the rank transform

A fundamental problem faced by stereo matching algorithms is the matching or correspondence problem. A wide range of algorithms have been proposed for the correspondence problem. For all matching algorithms, it would be useful to be able to compute a measure of the probability of correctness, or reliability of a match. This paper focuses in particular on one class for matching algorithms, which are based on the rank transform. The interest in these algorithms for stereo matching stems from their invariance to radiometric distortion, and their amenability to fast hardware implementation. This work differs from previous work in that it derives, from first principles, an expression for the probability of a correct match. This method was based on an enumeration of all possible symbols for matching. The theoretical results for disparity error prediction, obtained using this method, were found to agree well with experimental results. However, disadvantages of the technique developed in this chapter are that it is not easily applicable to real images, and also that it is too computationally expensive for practical window sizes. Nevertheless, the exercise provides an interesting and novel analysis of match reliability.