Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Adult
AC is characterised by a depth-dependent composition and structure of the extracellular matrix that results in depth-dependent
mechanical properties, important for the functions of adult AC. Collagen is the most abundant solid component and it affects
the mechanical behaviour of AC. The current objective is to quantify the postnatal development of depth-dependent collagen
density in sheep (Ovis aries) AC between birth and maturity. We use Fourier transform infra-red micro-spectroscopy to investigate collagen density in
48 sheep divided over ten sample points between birth (stillborn) and maturity (72 weeks). In each animal, we investigate
six anatomical sites (caudal, distal and rostral locations at the medial and lateral side of the joint) in the distal metacarpus
of a fore leg and a hind leg. 相似文献
The collagen fibril network is an important factor for the depth-dependent mechanical behaviour of adult articular cartilage
(AC). Recent studies show that collagen orientation is parallel to the articular surface throughout the tissue depth in perinatal
animals, and that the collagen orientations transform to a depth-dependent arcade-like structure in adult animals. Current
understanding on the mechanobiology of postnatal AC development is incomplete. In the current paper, we investigate the contribution
of collagen fibril orientation changes to the depth-dependent mechanical properties of AC. We use a composition-based finite
element model to simulate in a 1-D confined compression geometry the effects of ten different collagen orientation patterns
that were measured in developing sheep. In initial postnatal life, AC is mostly subject to growth and we observe only small
changes in depth-dependent mechanical behaviour. Functional adaptation of depth-dependent mechanical behaviour of AC takes
place in the second half of life before puberty. Changes in fibril orientation alone increase cartilage stiffness during development
through the modulation of swelling strains and osmotic pressures. Changes in stiffness are most pronounced for small stresses
and for cartilage adjacent to the bone. We hypothesize that postnatal changes in collagen fibril orientation induce mechanical
effects that in turn promote these changes. We further hypothesize that a part of the depth-dependent postnatal increase in
collagen content in literature is initiated by the depth-dependent postnatal increase in fibril strain due to collagen fibril
reorientation. 相似文献
A close relationship has been found between the 3D collagen structure and physiological condition of articular cartilage (AC). Studying the 3D collagen network in AC offers a way to determine the condition of the cartilage. However, traditional qualitative studies are time consuming and subjective. This study aims to develop a computer vision-based classifier to automatically determine the condition of AC tissue based on the structural characteristics of the collagen network. Texture analysis was applied to quantitatively characterise the 3D collagen structure in normal (International Cartilage Repair Society, ICRS, grade 0), aged (ICRS grade 1) and osteoarthritic cartilages (ICRS grade 2). Principle component techniques and linear discriminant analysis were then used to classify the microstructural characteristics of the 3D collagen meshwork and the condition of the AC. The 3D collagen meshwork in the three physiological condition groups displayed distinctive characteristics. Texture analysis indicated a significant difference in the mean texture parameters of the 3D collagen network between groups. The principle component and linear discriminant analysis of the texture data allowed for the development of a classifier for identifying the physiological status of the AC with an expected prediction error of 4.23%. An automatic image analysis classifier has been developed to predict the physiological condition of AC (from ICRS grade 0 to 2) based on texture data from the 3D collagen network in the tissue. 相似文献
Mesenchymal stem cells (MSC) are highly attractive for use in cartilage regeneration. To date, MSC are usually recruited from
subchondral bone marrow using microfracture. Recent data suggest that isolated cells from adult human articular cartilage,
which express the combination of the cell-surface markers CD105 and CD166, are multi-potent mesenchymal progenitor cells (MPC)
with characteristics similar to MSC. MPC within the cartilage matrix, the target of tissue regeneration, may provide the basis
for in situ regeneration of focal cartilage defects. However, there is only limited information concerning the presence/abundance
of CD105+/CD166+ MPC in human articular cartilage. The present study therefore assessed the relative percentage and particularly the zonal
distribution of cartilage MPC using the markers CD105/CD166. 相似文献
Collagen-like surface proteins Scl1 and Scl2 on Streptococcus pyogenes contain contiguous Gly-X-X triplet amino acid motifs, the characteristic structure of human collagen. Although the potential
role of Scl1 in adhesion has been studied, the conclusions may be affected by the use of different S. pyogenes strains and their carriages of various adhesins. To explore the bona fide nature of Scl1 in adherence to human epithelial cells without the potential interference of other streptococcal surface factors,
we constructed a scl1 isogenic mutant from the Scl2-defective S. pyogenes strain and a Scl1-expressed Escherichia coli. 相似文献
Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly
different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes
that could be used to distinguish bovine NP cells from AC and annulus fibrosus (AF) cells, and to further determine their
expression in normal and degenerate human intervertebral disc (IVD) cells. 相似文献
The intra-helical cleavage of type II collagen by proteases, including collagenases and cathepsin K, is increased with aging and osteoarthritis (OA) in cartilage as determined by immunochemical assays. The distinct sites of collagen cleavage generated by collagenases and cathepsin K in healthy and OA human femoral condylar cartilages were identified and compared.
Methods
Fixed frozen cartilage sections were examined immunohistochemically, using antibodies that react with the collagenase-generated cleavage neoepitopes, C2C and C1,2C, and the primary cleavage neoepitope (C2K) generated in type II collagen by the action of cathepsin K and possibly by other proteases, but not by any collagenases studied to date.
Results
In most cases, the staining patterns for collagen cleavage were similar for all three epitopes: weak to moderate mainly pericellular staining in non-OA cartilage from younger individuals and stronger, more widespread staining in aging and OA cartilages that often extended from the superficial to the mid/deep zone of the tissue. In very degenerate OA specimens, with significant disruption of the articular surface, staining was distributed throughout most of the cartilage matrix.
Conclusions
Cleavage of collagen by proteases usually arises pericellularly around chondrocytes at and near the articular surface, subsequently becoming more intense and extending progressively deeper into the cartilage with aging and OA. The close correspondence between the distributions of these products suggests that both collagenases and cathepsin K, and other proteases that may generate this distinct cathepsin K cleavage site, are usually active in the same sites in the degradation of type II collagen. 相似文献
Congenital diaphragmatic hernia (CDH) is a birth defect with significant morbidity and mortality. Knowledge of diaphragm morphogenesis
and the aberrations leading to CDH is limited. Although classical embryologists described the diaphragm as arising from the
septum transversum, pleuroperitoneal folds (PPF), esophageal mesentery and body wall, animal studies suggest that the PPF
is the major, if not sole, contributor to the muscular diaphragm. Recently, a posterior defect in the PPF has been identified
when the teratogen nitrofen is used to induce CDH in fetal rodents. We describe use of a cell-based computer modeling system
(Nudge++™) to study diaphragm morphogenesis. 相似文献
Collagen ultrastructure plays a central role in the function of a wide range of connective tissues. Studying collagen structure at the microscopic scale is therefore of considerable interest to understand the mechanisms of tissue pathologies. Here, we use second harmonic generation microscopy to characterize collagen structure within bone and articular cartilage in human knees. We analyze the intensity dependence on polarization and discuss the differences between Forward and Backward images in both tissues. Focusing on articular cartilage, we observe an increase in Forward/Backward ratio from the cartilage surface to the bone. Coupling these results to numerical simulations reveals the evolution of collagen fibril diameter and spatial organization as a function of depth within cartilage.
We evaluate the potential of paired isotopic analysis of bone carbonate and collagen to examine the diet of post-medieval human and animal populations from England (17th–19th c.), including, for the first time, manufacturing towns in northern England. The potential for identifying C4 crop consumption is explored alongside regional and local patterning in diet by sex and socioeconomic status.
Materials and Methods
Humans (n = 216) and animals (n = 168) were analyzed from sites in London and northern England for both carbon and nitrogen isotopes of bone collagen (𝛿13Ccoll, 𝛿15Ncoll). Isotopic analysis of bone carbonates (𝛿13Ccarb, 𝛿18Ocarb) was carried out on all humans and 27 animals, using Fourier transform infrared spectroscopy–attenuated total reflectance to assess diagenesis.
Results
Variations in diet were observed between and within different populations by geographical location and socioeconomic status. Three pigs and one cow consumed C4 resources, indicating the availability of C4-fed animal protein. Londoners consumed more animal and marine protein and C4 resources. Middle- and upper-class populations from both London and northern populations also had greater access to these foods compared to those of lower status in the same regions.
Discussion
This substantial multi-isotope dataset deriving from bone carbonate and collagen combined from diverse post-medieval urban communities enabled, for the first time, the biomolecular identification of the dynamics of C4 consumption (cane sugar/maize) in England, providing insight into the dynamics of food globalization during this period. We also add substantially to the animal dataset for post-medieval England, providing further insight into animal management during a key moment of agricultural change. 相似文献
In humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory
and signaling functions. Understanding these potentially important phenomena requires non-invasive measurements of collagen
network structure that can be performed in live animals or humans. The goal of this study was to show that ultrasound can
be used to quantify dynamic changes in local connective tissue structure in vivo. We first performed combined ultrasound and histology examinations of the same tissue in two subjects undergoing surgery:
in one subject, we examined the relationship of ultrasound to histological images in three dimensions; in the other, we examined
the effect of a localized tissue perturbation using a previously developed robotic acupuncture needling technique. In ten
additional non-surgical subjects, we quantified changes in tissue spatial organization over time during needle rotation vs.
no rotation using ultrasound and semi-variogram analyses. 相似文献
Oestrogen depletion may influence onset and/or progression of osteoarthritis. We investigated in an ovariectomized mouse model
the impact of oestrogen loss and oestrogen supplementation on articular cartilage and subchondral bone in tibia and patella,
and assessed bone changes in osteoarthritis development. 相似文献
Among mammalian soft tissues, articular cartilage is particularly interesting because it can endure a lifetime of daily mechanical loading despite having minimal regenerative capacity. This remarkable resilience may be due to the depth-dependent mechanical properties, which have been shown to localize strain and energy dissipation. This paradigm proposes that these properties arise from the depth-dependent collagen fiber orientation. Nevertheless, this structure-function relationship has not yet been quantified. Here, we use confocal elastography, quantitative polarized light microscopy, and Fourier-transform infrared imaging to make same-sample measurements of the depth-dependent shear modulus, collagen fiber organization, and extracellular matrix concentration in neonatal bovine articular cartilage. We find weak correlations between the shear modulus |G∗| and both the collagen fiber orientation and polarization. We find a much stronger correlation between |G∗| and the concentration of collagen fibers. Interestingly, very small changes in collagen volume fraction vc lead to orders-of-magnitude changes in the modulus with |G∗| scaling as (vc – v0)ξ. Such dependencies are observed in the rheology of other biopolymer networks whose structure exhibits rigidity percolation phase transitions. Along these lines, we propose that the collagen network in articular cartilage is near a percolation threshold that gives rise to these large mechanical variations and localization of strain at the tissue’s surface. 相似文献
Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine
the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation
(Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage. 相似文献
The rheumatoid arthritis (RA) synovium is characterised by the presence of an aggressive population of activated synovial
fibroblasts (RASFs) that are prominently involved in the destruction of articular cartilage and bone. Accumulating evidence
suggests that RASFs are relatively resistant to Fas-ligand (FasL)-induced apoptosis, but the data concerning tumour necrosis
factor-related apoptosis-inducing ligand (TRAIL) have been conflicting. Here, we hypothesise that the susceptibility of RASFs
to receptor-mediated apoptosis depends on the proliferation status of these cells and therefore analysed the cell cycle dependency
of FasL- and TRAIL-induced programmed cell death of RASFs in vitro. 相似文献
Osteoprotegerin (OPG) has been reported to prevent bone resorption by inhibiting the formation, function, and survival of
osteoclasts in a variety of animal models. However, the effects of OPG on bone metabolism in avian species have not been described.
The objective of this study was to investigate the effects of chicken OPG (chOPG) expressed in chicken embryo fibroblasts
(CEFs) on chicken osteoclast function in vitro. 相似文献
There is an ever-increasing need for animal models to evaluate efficacy and safety of new therapeutics in the field of rheumatoid
arthritis (RA). Particularly for the early preclinical evaluation of human-specific biologicals targeting the progressive
phase of the disease, there is a need for relevant animal models. In response to this requirement we set out to develop a
model of collagen-induced arthritis (CIA) in a small-sized nonhuman primate species (300 to 400 g at adult age); that is,
the common marmoset (Callithrix jacchus). 相似文献
Among mammalian soft tissues, articular cartilage is particularly interesting because it can endure a lifetime of daily mechanical loading despite having minimal regenerative capacity. This remarkable resilience may be due to the depth-dependent mechanical properties, which have been shown to localize strain and energy dissipation. This paradigm proposes that these properties arise from the depth-dependent collagen fiber orientation. Nevertheless, this structure-function relationship has not yet been quantified. Here, we use confocal elastography, quantitative polarized light microscopy, and Fourier-transform infrared imaging to make same-sample measurements of the depth-dependent shear modulus, collagen fiber organization, and extracellular matrix concentration in neonatal bovine articular cartilage. We find weak correlations between the shear modulus |G∗| and both the collagen fiber orientation and polarization. We find a much stronger correlation between |G∗| and the concentration of collagen fibers. Interestingly, very small changes in collagen volume fraction vc lead to orders-of-magnitude changes in the modulus with |G∗| scaling as (vc – v0)ξ. Such dependencies are observed in the rheology of other biopolymer networks whose structure exhibits rigidity percolation phase transitions. Along these lines, we propose that the collagen network in articular cartilage is near a percolation threshold that gives rise to these large mechanical variations and localization of strain at the tissue’s surface. 相似文献
To compare the potential of adult and fetal animals to repair articular cartilage, we investigated the early process after creating superficial defects in the femoral knee cartilage in rat models. In fetuses at 19 days of gestation, both chondrocytes and the extracellular matrix responded notably by 48 h after artificial injury. Staining patterns with safranin O revealed that, by 1 h after injury, some components of the extracellular matrix around the wound were modified, and the change spread from the limited region to the entire knee cartilage within 24 h. The chondrocytes in the area surrounding the wound transiently expressed increased level of c-fos from 1 h to 6 h. The wound remained 1 day after birth, i.e., 72 h after injury, but was completely repaired 10 days after birth. In contrast, neither visible responses nor transient c-fos expression was observed in 12-week-old adult articular cartilage 48 h after injury. We also examined the relationships between the intracellular Ca2+ concentration ([Ca2+]i) and the induction of c-fos expression in the cartilage. Applications of ATP or Ca2+ ionophore A23187, both of which increase [Ca2+]i, induced immediate expression of c-fos in primary cultured chondrocytes: 1 M ATP elicited an increase of [Ca2+]i in chondrocytes in fetal cartilage slices, but 1 mM was required in adult cartilage slices. Our findings show the presence of a signaling pathway that is apparently active in the repair of fetal but not adult articular cartilage and that involves the intercellular transfer of ATP, increase of [Ca2+]i, and expression of c-fos in cartilage.This study was supported in part by Health Sciences Research Grants for Research on Human Genome, Tissue Engineering and Food Biotechnology to M.O. from the Japanese Ministry of Health, Labor and Welfare 相似文献