Modelling external bone adaptation using evolutionary structural optimisation

External remodelling is significant in the bone healing process, and it is essential to predict the bone external shape in the design of artificial bone grafts. This paper demonstrates the effectiveness of the evolutionary structural optimisation (ESO) method for the simulation of bone morphology. A two-dimensional ESO strategy is developed which is capable of finding the modified bone topology beginning with any geometry under any loading conditions. The morphology of bone structure is described by the quantitative bone adaptation theory, which is integrated with the finite element method. The evolutionary topology optimisation process is introduced to find the bone shape. A rectangle, which occupies a larger space than the external shape of the bone structure, is specified as a design domain; the evolutionary process iteratively eliminates and redistributes material throughout the domain to obtain an optimum arrangement of bone materials. The technique has been tested on a wide range of examples. In this paper, the formation of trabecular bone architecture around an implant is studied; as another example, the growth of the coronal section of a vertebral body is predicted. The examples support the assertion that the external shape of bone structure can be successfully predicted by the proposed ESO procedure.     

sec24d encoding a component of COPII is essential for vertebra formation, revealed by the analysis of the medaka mutant, vbi

We characterized a medaka mutant, vertebra imperfecta (vbi), that displays skeletal defects such as craniofacial malformation and delay of vertebra formation. Positional cloning analysis revealed a nonsense mutation in sec24d encoding a component of the COPII coat that plays a role in anterograde protein trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus. Immunofluorescence analysis revealed the accumulation of type II collagen in the cytoplasm of craniofacial chondrocytes, notochord cells, and the cells on the myoseptal boundary in vbi mutants. Electron microscopy analysis revealed dilation of the ER and defective secretion of ECM components from cells in both the craniofacial cartilage and notochord in vbi. The higher vertebrates have at least 4 sec24 paralogs; however, the function of each paralog in development remains unknown. sec24d is highly expressed in the tissues that are rich in extracellular matrix and is essential for the secretion of ECM component molecules leading to the formation of craniofacial cartilage and vertebra.     

Mesh-morphing algorithms for specimen-specific finite element modeling

Despite recent advances in software for meshing specimen-specific geometries, considerable effort is still often required to produce and analyze specimen-specific models suitable for biomechanical analysis through finite element modeling. We hypothesize that it is possible to obtain accurate models by adapting a pre-existing geometry to represent a target specimen using morphing techniques. Here we present two algorithms for morphing, automated wrapping (AW) and manual landmarks (ML), and demonstrate their use to prepare specimen-specific models of caudal rat vertebrae. We evaluate the algorithms by measuring the distance between target and morphed geometries and by comparing response to axial loading simulated with finite element (FE) methods.

First a traditional reconstruction process based on μCT was used to obtain two natural specimen-specific FE models. Next, the two morphing algorithms were used to compute mappings from the surface of one model, the source, to the other, the target, and to use this mapping to morph the source mesh to produce a target mesh. The μCT images were then used to assign element-specific material properties. In AW the mappings were obtained by wrapping the source and target surfaces with an auxiliary triangulated surface. In ML, landmarks were manually placed on corresponding locations on the surfaces of both source and target.

Both morphing algorithms were successful in reproducing the shape of the target vertebra with a median distance between natural and morphed models of 18.8 and 32.2 μm, respectively, for AW and ML. Whereas AW–morphing produced a surface more closely resembling that of the target, ML guaranteed correspondence of the landmark locations between source and target. Morphing preserved the quality of the mesh producing models suitable for FE simulation. Moreover, there were only minor differences between natural and morphed models in predictions of deformation, strain and stress. We therefore conclude that it is possible to use mesh-morphing techniques to produce accurate specimen-specific FE models of caudal rat vertebrae. Mesh morphing techniques provide advantages over conventional specimen-specific finite element modeling by reducing the effort required to generate multiple target specimen models, facilitating intermodel comparisons through correspondence of nodes and maintenance of connectivity, and lends itself to parametric evaluation of “artificial” geometries with a focus on optimizing reconstruction.     

Development of the vertebral morphogenetic field in the mouse: interactions between Crossveinless-2 and Twisted Gastrulation

Crossveinless-2 (Cv2), Twisted Gastrulation (Tsg) and Chordin (Chd) are components of an extracellular biochemical pathway that regulates Bone Morphogenetic Protein (BMP) activity during dorso-ventral patterning of Drosophila and Xenopus embryos, the formation of the fly wing, and mouse skeletogenesis. Because the nature of their genetic interactions remained untested in the mouse, we generated a null allele for Cv2 which was crossed to Tsg and Chd mutants to obtain Cv2; Tsg and Cv2; Chd compound mutants. We found that Cv2 is essential for skeletogenesis as its mutation caused the loss of multiple bone structures and posterior homeotic transformation of the last thoracic vertebra. During early vertebral development, Smad1 phosphorylation in the intervertebral region was decreased in the Cv2 mutant, even though CV2 protein is normally located in the future vertebral bodies. Because Cv2 mutation affects BMP signaling at a distance, this suggested that CV2 is involved in the localization of the BMP morphogenetic signal. Cv2 and Chd mutations did not interact significantly. However, mutation of Tsg was epistatic to all CV2 phenotypes. We propose a model in which CV2 and Tsg participate in the generation of a BMP signaling morphogenetic field during vertebral formation in which CV2 serves to concentrate diffusible Tsg/BMP4 complexes in the vertebral body cartilage.     

我国沿海拟虎鲸骨骼研究

本文对我国沿海所捕获的拟虎鲸骨骼系统,进行了较全面的研究和测量,并对其骨骼特点及形态、功能方面也做了些探讨。     

A col10a1:nlGFP transgenic line displays putative osteoblast precursors at the medaka notochordal sheath prior to mineralization

In teleosts, such as medaka, ossification of the vertebral column starts with the mineralization of the notochordal sheath in a segmental pattern. This establishes the chordal centrum, which serves as the basis for further ossifications by sclerotome derived osteoblasts generating the vertebral body. So far, it is unclear which cells produce the notochordal sheath and how a segmental pattern of mineralization is established in teleosts. Here, we use a transgenic medaka line that expresses nlGFP under the control of the col10a1 promoter for in vivo analysis of vertebral body formation. We show that col10a1:nlGFP expression recapitulates endogenous col10a1 expression. In the axial skeleton, col10a1:nlGFP cells appear prior to the mineralization of the notochordal sheath in a segmental pattern. These cells remain on the outer surface of the chordal centra during mineralization as well as subsequent perichordal ossification of the vertebral bodies. Using twist1a1:dsRed and osx:mCherry transgenic lines we show that a subset of col10a1:nlGFP cells is derived from sclerotomal precursors and differentiates into future osteoblasts. For the first time, this shows a segmental occurrence of putative osteoblast precursors in the vertebral centra prior to ossification of the notochordal sheath. This opens the possibility that sclerotome derived cells in teleosts are implicated in the establishment of the mineralized vertebral column in a similar manner as previously described for tetrapods.     

Vertebral lesions in a titanosaurian dinosaur from the Lower-Upper Cretaceous of Brazil

In this paper we describe macroscopically two types of bone lesions on a caudal vertebra of an indeterminate titanosaur recovered from the Lower-Upper Cretaceous (Albian-Cenomanian) Açu Formation in the Potiguar Basin, Brazil. The first type of lesion corresponds to cystic lesions on cranial and caudal joint surfaces of the vertebral body, which are identified as subchondral cysts. The second type of lesion corresponds to an irregular bone overgrowth located on longitudinal ligament insertion points. This ossification can be associated with an axial spondyloarthropathy or diffuse idiopathic skeletal hyperostosis (DISH). Bone overgrowth on vertebrae is well documented in the dinosaur fossil record, whereas this is only the second case recorded of subchondral cysts.     

Statistical shape modeling characterizes three-dimensional shape and alignment variability in the lumbar spine

The mechanics of the lumbar spine are heavily dependent on the underlying anatomy. Anatomical measures are used to assess the progression of pathologies related to low back pain and to screen patients for surgical treatment options. To describe anatomical norms and pathological differences for the population, statistical shape modeling, which uses full three-dimensional representations of bone morphology and relative alignment, can capture intersubject variability and enable comparative evaluations of subject to population. Accordingly, the objective of this study was to develop a comprehensive set of three-dimensional statistical models to characterize anatomical variability in the lumbar spine, by specifically describing the shape of individual vertebrae, and shape and alignment of the entire lumbar spine (L1-S1), with a focus on the L4-L5 and L5-S1 functional spinal units (FSU). Using CT scans for a cohort of 52 patients, lumbar spine geometries were registered to a template to establish correspondence and a principal component analysis identified the primary modes of variation. Scaling was the most prevalent mode of variation for all models. Subsequent modes of the statistical shape models of the individual bones characterized shape variation within the processes. Subsequent modes of variation for the FSU and entire spine models described alignment changes associated with disc height and lordosis. Quantification of anatomical variation in the spine with statistical models can inform implant design and sizing, assist clinicians in diagnosing pathologies, screen patients for treatment options, and support pre-operative planning.     

大渡河上游麻尔柯河高原鳅的年龄与生长

研究了采自大渡河上游麻尔柯河及其支流则曲的129尾麻尔柯河高原鳅(Triplophysa markehenensis)的年龄结构和生长特性。结果表明,耳石和脊椎骨都可作为年龄鉴定的材料,其中耳石是进行年龄鉴定的最适材料,脊椎骨则可作为辅助材料;背鳍条不适合用于年龄鉴定。这批麻尔柯河高原鳅的年龄范围为2～8龄,以3～6龄居多,占总数的83.5%;体长体重呈幂函数关系:W=0.000015L2.951931;Von Bertalanffy生长方程为:Lt=173.1241[1-e-0.1597(t+0.5328)],Wt=60.7531[1-e-0.1597(t+0.5328)]2.9519;体重生长曲线的拐点为t=6.25,拐点时体长为114.5mm,体重为17.9g。关键词:耳石;脊椎骨;年龄;生长     

Age-independent constancy of mineral contents in human vertebra and auditory ossicle

To elucidate age-related changes of mineral contents in human bones, element contents of human vertebrae and auditory ossicles were determined by inductively coupled plasma atomic-emission spectrometry. The cervical, thoracic, and lumbar vertebrae were removed from 12 vertebral columns. The mallei of auditory ossicle were removed from 27 cadavers. It was found that average relative contents (RCs) of calcium and phosphorus in cervical, thoracic, and lumbar vertebrae remained almost constant within ages ranging from 46 to 99 y. In addition, it was found that the RCs of calcium and phosphorus in men’s and women’s mallei remained constant within ages ranging from 40 to 98 yr. These results support the view that there is no significant agedependent change of mineral contents in human bones.