Layer Of Articular Cartilage Research Articles

Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing.

Arthroplasty is currently the only surgical procedure available to restore joint function following articular cartilage and bone degeneration associated with diseases such as osteoarthritis (OA). A potential alternative to this procedure would be to tissue-engineer a biological implant and use it to replace the entire diseased joint. The objective of this study was therefore to tissue-engineer a scaled-up, anatomically shaped, osteochondral construct suitable for partial or total resurfacing of a diseased joint. To this end it was first demonstrated that a bone marrow derived mesenchymal stem cell seeded alginate hydrogel could support endochondral bone formation in vivo within the osseous component of an osteochondral construct, and furthermore, that a phenotypically stable layer of articular cartilage could be engineered over this bony tissue using a co-culture of chondrocytes and mesenchymal stem cells. Co-culture was found to enhance the in vitro development of the chondral phase of the engineered graft and to dramatically reduce its mineralisation in vivo. In the final part of the study, tissue-engineered grafts (~ 2 cm diameter) mimicking the geometry of medial femorotibial joint prostheses were generated using laser scanning and rapid prototyped moulds. After 8 weeks in vivo, a layer of cartilage remained on the surface of these scaled-up engineered implants, with evidence of mineralisation and bone development in the underlying osseous region of the graft. These findings open up the possibility of a tissue-engineered treatment option for diseases such as OA.

An asymptotic model for a thin biphasic poroviscoelastic layer: Fig. 1

Summary A three-dimensional deformation problem for articular cartilage layer is considered in the framework of the linear biphasic poroviscoelastic theory. The solid matrix of biphasic layer is assumed to be transversely isotropic. A short-time leading-order asymptotic solution is obtained for a relatively thin biphasic poroviscoelastic layer bonded to a rigid impermeable substrate.

Measuring microscale strain fields in articular cartilage during rapid impact reveals thresholds for chondrocyte death and a protective role for the superficial layer

Articular cartilage is a heterogeneous soft tissue that dissipates and distributes loads in mammalian joints. Though robust, cartilage is susceptible to damage from loading at high rates or magnitudes. Such injurious loads have been implicated in degenerative changes, including chronic osteoarthritis (OA), which remains a leading cause of disability in developed nations. Despite decades of research, mechanisms of OA initiation after trauma remain poorly understood. Indeed, although bulk cartilage mechanics are measurable during impact, current techniques cannot access microscale mechanics at those rapid time scales. We aimed to address this knowledge gap by imaging the microscale mechanics and corresponding acute biological changes of cartilage in response to rapid loading. In this study, we utilized fast-camera and confocal microscopy to achieve roughly 85µm spatial resolution of both the cartilage deformation during a rapid (~3ms), localized impact and the chondrocyte death following impact. Our results showed that, at these high rates, strain and chondrocyte death were highly correlated (p<0.001) with a threshold of 8% microscale strain norm before any cell death occurred. Additionally, chondrocyte death had developed by two hours after impact, suggesting a time frame for clinical therapeutics. Moreover, when the superficial layer was removed, strain – and subsequently chondrocyte death – penetrated deeper into the samples (p<0.001), suggesting a protective role for the superficial layer of articular cartilage. Combined, these results provide insight regarding the detailed biomechanics that drive early chondrocyte damage after trauma and emphasize the importance of understanding cartilage and its mechanics on the microscale.

A quantitative interpretation of the response of articular cartilage to atomic force microscopy-based dynamic nanoindentation tests.

In this paper, a quantitative interpretation for atomic force microscopy-based dynamic nanoindentation (AFM-DN) tests on the superficial layers of bovine articular cartilage (AC) is provided. The relevant constitutive parameters of the tissue are estimated by fitting experimental results with a finite element model in the frequency domain. Such model comprises a poroelastic stress-strain relationship for a fibril reinforced tissue constitution, assuming a continuous distribution of the collagen network orientations. The identification procedure was first validated using a simplified transversely isotropic constitutive relationship; then, the experimental data were manually fitted by using the continuous distribution fibril model. Tissue permeability is derived from the maximum value of the phase shift between the input harmonic loading and the harmonic tissue response. Tissue parameters related to the stiffness are obtained from the frequency response of the experimental storage modulus and phase shift. With this procedure, an axial to transverse stiffness ratio (anisotropy ratio) of about 0.15 is estimated.

Effects of low tangential permeability in the superficial layer on the frictional property of articular cartilage

Abstract The biphasic characteristics of articular cartilage are known to play important roles in cartilage lubrication. However, it is still difficult to biotribologically explain the extremely low friction coefficient observed in articular cartilage. Previous studies have indicated that the surface layer of articular cartilage includes tangentailly-aligned dense collagen fibers while permeability of articular cartilage in tangential direction is dramatically reduced in response to compressive strain. Therefore, we hypothesized that the anisotropic structure and property in articular cartilage surface improve the lubrication and frictional properties. A fiber–reinforced poroelastic biphasic model was developed in Abaqus to determine the effect of low tangential permeability on the frictional property of articular cartilage. In the model, the tangential permeability in the superficial layer of 100 μm in thickness was reduced to 1/10 as compared with normal permeability. Results revealed that the permeability-reduced superficial layer plays an important role in decreasing friction coefficient in articular cartilage and the role is more significant in slower friction including the start-up friction. Results also revealed that there is a positive effect of the thickness of the low permeability layer on the start-up friction property, while the effect was almost negligible on the dynamic friction property.

The effect of graft strength on knee laxity and graft in-situ forces after posterior cruciate ligament reconstruction.

Surgical reconstruction is generally recommended for posterior cruciate ligament (PCL) injuries; however, the use of grafts is still a controversial problem. In this study, a three-dimensional finite element model of the human tibiofemoral joint with articular cartilage layers, menisci, and four main ligaments was constructed to investigate the effects of graft strengths on knee kinematics and in-situ forces of PCL grafts. Nine different graft strengths with stiffness ranging from 0% (PCL rupture) to 200%, in increments of 25%, of an intact PCL’s strength were used to simulate the PCL reconstruction. A 100 N posterior tibial drawer load was applied to the knee joint at full extension. Results revealed that the maximum posterior translation of the PCL rupture model (0% stiffness) was 6.77 mm in the medial compartment, which resulted in tibial internal rotation of about 3.01°. After PCL reconstruction with any graft strength, the laxity of the medial tibial compartment was noticeably improved. Tibial translation and rotation were similar to the intact knee after PCL reconstruction with graft strengths ranging from 75% to 125% of an intact PCL. When the graft’s strength surpassed 150%, the medial tibia moved forward and external tibial rotation greatly increased. The in-situ forces generated in the PCL grafts ranged from 13.15 N to 75.82 N, depending on the stiffness. In conclusion, the strength of PCL grafts have has a noticeable effect on anterior-posterior translation of the medial tibial compartment and its in-situ force. Similar kinematic response may happen in the models when the PCL graft’s strength lies between 75% and 125% of an intact PCL.

Identification of a Prg4-expressing articular cartilage progenitor cell population in mice.

To generate knockin mice that express a tamoxifen-inducible Cre recombinase from the Prg4 locus (Prg4(GFPCreERt2) mice) and to use these animals to fate-map the progeny of Prg4-positive articular cartilage cells at various ages. We crossed Prg4(GFPCreERt2) mice with Rosa26(floxlacZ) or Rosa26(mTmG) reporter strains, admin-istered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre-mediated recom-bination by histochemistry and/or fluorescence microscopy. In 1-month-old mice, the expression of the Prg4(GFPCreERt2) allele mirrored the expression of endogenous Prg4 and, when tamoxifen was admin-istered for 10 days, caused Cre-mediated recombination in ∼70% of the superficial-most chondrocytes. Prg4(GFPCreERt2)-expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1-month-old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, Prg4(GFPCreERt2)-expressing cells were largely restricted to the superficial-most cell layer of the forming joint, yet at ∼1 year, the progeny of these cells spanned the depth of the articular cartilage. Our results suggest that Prg4-expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that Prg4(GFPCreERt2) is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The Prg4(GFPCreERt2) allele should be a useful tool for inducing efficient Cre-mediated recombination of loxP-flanked alleles at sites of Prg4 expression.

Age-Independent Cartilage Generation for Synovium-Based Autologous Chondrocyte Implantation.

The articular cartilage layer of synovial joints is commonly lesioned by trauma or by a degenerative joint disease. Attempts to repair the damage frequently involve the performance of autologous chondrocyte implantation (ACI). Healthy cartilage must be first removed from the joint, and then, on a separate occasion, following the isolation of the chondrocytes and their expansion in vitro, implanted within the lesion. The disadvantages of this therapeutic approach include the destruction of healthy cartilage-which may predispose the joint to osteoarthritic degeneration-the necessarily restricted availability of healthy tissue, the limited proliferative capacity of the donor cells-which declines with age-and the need for two surgical interventions. We postulated that it should be possible to induce synovial stem cells, which are characterized by high, age-independent, proliferative and chondrogenic differentiation capacities, to lay down cartilage within the outer juxtasynovial space after the transcutaneous implantation of a carrier bearing BMP-2 in a slow-release system. The chondrocytes could be isolated on-site and immediately used for ACI. To test this hypothesis, Chinchilla rabbits were used as an experimental model. A collagenous patch bearing BMP-2 in a slow-delivery vehicle was sutured to the inner face of the synovial membrane. The neoformed tissue was excised 5, 8, 11 and 14 days postimplantation for histological and histomorphometric analyses. Neoformed tissue was observed within the outer juxtasynovial space already on the 5th postimplantation day. It contained connective and adipose tissues, and a central nugget of growing cartilage. Between days 5 and 14, the absolute volume of cartilage increased, attaining a value of 12 mm(3) at the latter juncture. Bone was deposited in measurable quantities from the 11th day onwards, but owing to resorption, the net volume did not exceed 1.5 mm(3) (14th day). The findings confirm our hypothesis. The quantity of neoformed cartilage that is deposited after only 1 week within the outer juxtasynovial space would yield sufficient cells for ACI. Since the BMP-2-bearing patches would be implanted transcutaneously in humans, only one surgical or arthroscopic intervention would be called for. Moreover, most importantly, sufficient numbers of cells could be generated in patients of all ages.

Tissue Engineering Whole Bones Through Endochondral Ossification: Regenerating the Distal Phalanx.

Novel strategies are urgently required to facilitate regeneration of entire bones lost due to trauma or disease. In this study, we present a novel framework for the regeneration of whole bones by tissue engineering anatomically shaped hypertrophic cartilaginous grafts in vitro that subsequently drive endochondral bone formation in vivo. To realize this, we first fabricated molds from digitized images to generate mesenchymal stem cell-laden alginate hydrogels in the shape of different bones (the temporomandibular joint [TMJ] condyle and the distal phalanx). These constructs could be stimulated in vitro to generate anatomically shaped hypertrophic cartilaginous tissues that had begun to calcify around their periphery. Constructs were then formed into the shape of the distal phalanx to create the hypertrophic precursor of the osseous component of an engineered long bone. A layer of cartilage engineered through self-assembly of chondrocytes served as the articular surface of these constructs. Following chondrogenic priming and subcutaneous implantation, the hypertrophic phase of the engineered phalanx underwent endochondral ossification, leading to the generation of a vascularized bone integrated with a covering layer of stable articular cartilage. Furthermore, spatial bone deposition within the construct could be modulated by altering the architecture of the osseous component before implantation. These findings open up new horizons to whole limb regeneration by recapitulating key aspects of normal bone development.

The healing stages of an intramedullary implanted tibia: A stress strain comparative analysis of the calcification process

AimsThe extended usage of unreamed tibial nailing resulted in reports of an increased rate of complications, especially for the distal portion of the tibia. Unreamed nailing favours biology at the expense of the achievable mechanical stability, it is therefore of interest to define the limits of the clinical indications for this method. Extra-articular fractures of the distal tibial metaphysis, meta-diaphyseal junction, and adjacent diaphysis are distinct in their management from impaction derived ‘‘pilon’’ type fractures and mid-diaphyseal fractures. The goals of this work were to gain a thorough understanding of the load-sharing mechanism between unreamed nail and bones in a fractured tibia. With this purpose a complete model of the human leg was realised, simulating a mid-diaphyseal fracture, classified as A2 type 1, according to the AO classification.The analysis of the entire chain allows to have a complete picture of the stress distribution and of the most stressed bones and soft tissues, but, more importantly can overcome problems connected with boundary conditions imposed at single bony components. MethodsModel consists of six bony structures: pelvis, femur, patella, fibula, tibia, and a simplified lump of the feet, configured in a standing up position. Their articular cartilage layers, were simulated by 3D membranes of opportune stiffness connecting the different segments. Moreover an unreamed intra-medullary nail Expert Tibial Nail (DePuy Synthes®) stabilized the fractured tibia. A load of 700 N has been applied at the top of pelvis and a part the feet, at the tip, was rigidly fixed. Five different contact interfaces have been imposed at the different bony surfaces in contact. ResultsThree different conditions were analysed: the initially healthy tibia, the A2 type 1 fractured tibia with the Expert tibial nail implanted, and the follow up stage after complete healing of tibia. Non-linear finite element analysis of the models were performed with Abaqus version 5.4 (Hibbitt, Karlsson and Sorensen, Inc., Pawtucket, RI) using the geometric non linearity and automatic time stepping options. ConclusionThe obtained results reveal interesting consequences deriving by taking into account how the stress shielding can influence the integrity and resistance of bones, in order to identify the mechanical reasons for the unfavourable clinical results, and to identify borderline indications due to biomechanical factors. The evolution of treatment options for these fractures has been closely linked to developments in implant technology and surgical technique. Further developments in this area, particularly with respect to minimally invasive plating techniques and nail design are ongoing.

Short-term consolidation of articular cartilage in the long-term context of osteoarthritis.

Over ten percent of the population are afflicted by osteoarthritis, a chronic disease of diarthrodial joints such as the knees and hips, costing hundreds of billions of dollars every year. In this condition, the thin layers of articular cartilage on the bones degrade and weaken over years, causing pain, stiffness and eventual immobility. The biggest controllable risk factor is long-term mechanical overloading of the cartilage, but the disparity in time scales makes this process a challenge to model: loading events can take place every second, whereas degradation occurs over many months. Therefore, a suitable model must be sufficiently simple to permit evaluation over long periods of variable loading, yet must deliver results sufficiently accurate to be of clinical use, conditions unmet by existing models. To address this gap, we construct a two-component poroelastic model endowed with a new flow restricting boundary condition, which better represents the joint space environment compared to the typical free-flow condition. Under both static and cyclic loading, we explore the rate of gradual consolidation of the medium. In the static case, we analytically characterise the duration of consolidation, which governs the duration of effective fluid-assisted lubrication. In the oscillatory case, we identify a region of persistent strain oscillations in otherwise consolidated tissue, and derive estimates of its depth and magnitude. Finally, we link the two cases through the concept of an equivalent static stress, and discuss how our results help explain the inexorable cartilage degeneration of osteoarthritis.

The influence of altered occlusion on pro-inflammatory cytokine levels in the TMJ synovial tissues of rats

ObjectiveThe aim of this study was to evaluate whether altered occlusion affects both the condylar cartilage thickness and the cytokine levels of the TMJs of rats. DesignThirty adult-male rats (n=30) were randomly assigned to three experimental conditions: a control group that underwent sham operations with unaltered occlusion; an FPDM group that underwent functional posterior displacement of the mandible that was induced by an incisor guiding appliance; and an iOVD group in which the increased occlusal vertical dimension was induced in the molars. The rats were subjected to the FPDM or iOVD model for 14 days and then killed. Both the right and left TMJs were removed and randomly assigned to examination with staining or immunoassay techniques. Toluidine blue staining was used to measure the thicknesses of the four layers of the articular cartilage (i.e., the fibrous, proliferating, mature, and hypertrophic layers). ELISA assays were used to assess the concentrations of the pro-inflammatory cytokines IL-1α, IL-1β, IL-6, and tumour necrosis factor (TNF-α). The measurements of the articular cartilage layers and cytokine concentrations were analyzed with ANOVA and Tukey's tests and Kruskal–Wallis and Dunn tests, respectively (α=5%). ResultsThe thickness of articular cartilage in the FPDM group (0.3±0.03mm) was significantly greater than those of the control (0.2±0.01mm) and iOVD (0.25±0.03mm) groups. No significant difference was observed between the control and iOVD groups. The four articular cartilage layers were thicker in the FPDM group than in the control and iOVD groups, and the latter two groups did not differ one from each other. Both the FPDM and iOVD groups exhibited higher cytokine levels than did the control (p<0.05) group. Compared to the FPDM group, the iOVD group exhibited significantly higher levels of IL-1β and TNF-α. ConclusionBoth models induced inflammation in the TMJ and caused significant structural changes in the TMJ and surrounding tissues.

Reconstruction of Hyaline Cartilage Deep Layer Properties in 3-Dimensional Cultures of Human Articular Chondrocytes

Background:Articular cartilage (AC) injuries and malformations are commonly noticed because of trauma or age-related degeneration. Many methods have been adopted for replacing or repairing the damaged tissue. Currently available AC repair methods, in several cases, fail to yield good-quality long-lasting results, perhaps because the reconstructed tissue lacks the cellular and matrix properties seen in hyaline cartilage (HC).Purpose:To reconstruct HC tissue from 2-dimensional (2D) and 3-dimensional (3D) cultures of AC-derived human chondrocytes that would specifically exhibit the cellular and biochemical properties of the deep layer of HC.Study Design:Descriptive laboratory study.Methods:Two-dimensional cultures of human AC–derived chondrocytes were established in classical medium (CM) and newly defined medium (NDM) and maintained for a period of 6 weeks. These cells were suspended in 2 mm–thick collagen I gels, placed in 24-well culture inserts, and further cultured up to 30 days. Properties of chondrocytes, grown in 2D cultures and the reconstructed 3D cartilage tissue, were studied by optical and scanning electron microscopic techniques, immunohistochemistry, and cartilage-specific gene expression profiling by reverse transcription polymerase chain reaction and were compared with those of the deep layer of native human AC.Results:Two-dimensional chondrocyte cultures grown in NDM, in comparison with those grown in CM, showed more chondrocyte-specific gene activity and matrix properties. The NDM-grown chondrocytes in 3D cultures also showed better reproduction of deep layer properties of HC, as confirmed by microscopic and gene expression analysis. The method used in this study can yield cartilage tissue up to approximately 1.6 cm in diameter and 2 mm in thickness that satisfies the very low cell density and matrix composition properties present in the deep layer of normal HC.Conclusion:This study presents a novel and reproducible method for long-term culture of AC-derived chondrocytes and reconstruction of cartilage tissue with properties similar to the deep layer of HC in vitro.Clinical Relevance:The HC tissue obtained by the method described can be used to develop an implantable product for the replacement of damaged or malformed AC, especially in younger patients where the lesions are caused by trauma or mechanical stress.

PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis

To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit invivo. Daily subcutaneous injections of 10μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P<0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P<0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P=0.026) and enhanced mineral density of the subarticular spongiosa (P=0.001). Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis.

Lipid distribution in human knee and hip articular cartilage correlated to tissue surface roughness and surface active phospholipid layer presence: evidence of cooperative interfacial lipid delivery mechanisms

Lipid distribution in human knee and hip articular cartilage correlated to tissue surface roughness and surface active phospholipid layer presence: evidence of cooperative interfacial lipid delivery mechanisms

Cultivation of Human Chondrocytes on Cartilage Fluff Matrix without Loss of Phenotypic Expression

Chondrocytes grown from cartilage explants and then cultured with rehydrated previously desiccated thin strands of cartilage called “cartilage fluff matrix” or “fluff” filled the gaps between the strands of fluff making new cartilage and invaded the cartilage strands. The cells stained similar to the deep layers of normal articular cartilage though at least 60 days of culture. The chondrocytes binded the cartilage strands together and filled the gaps with new cartilage creating a solid construct.

Human Developmental Chondrogenesis as a Basis for Engineering Chondrocytes from Pluripotent Stem Cells

SummaryJoint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166low/negCD146low/negCD73+CD44lowBMPR1B+) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5–6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166low/negBMPR1B+ putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.

Meniscectomy: indications, procedure, outcomes, and rehabilitation

Meniscectomy: indications, procedure, outcomes, and rehabilitation Hermann Anetzberger,1 Christof Birkenmaier,2 Stephan Lorenz3 1Orthopädische Gemeinschaftspraxis am OEZ, Munich, Germany; 2Department of Orthopedics, Ludwig-Maximilian-University Munich, Munich, Germany; 3Department of Orthopedic Sports Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany Abstract: Meniscal injuries are among the most frequent reasons for knee problems. The goal of this manuscript is to review the biomechanical relevance of the human knee's menisci in relation to surgical indications, surgical techniques, rehabilitation, and outcomes. In order to identify the relevant literature, we performed a PubMed search for the years ranging from 1980–2013 using the following search terms: meniscus; biomechanical function; meniscectomy; meniscal repair; and clinical outcome. The meniscus helps to distribute the forces between the tibial and femoral articular cartilage layers in a load-sharing capacity. Meniscus damage or meniscectomy intuitively leads to an overloading of the cartilage and, hence, to the development of osteoarthrosis. Precise knowledge of meniscal shape and function, of the type of injury, of surgical techniques, as well as of postsurgical rehabilitative care are of decisive importance for an individually-adjusted treatment strategy. Other underlying coexisting knee pathologies also need to be considered. The diagnosis of a meniscal injury is based upon clinical history, physical examination, and imaging studies. The treatment of a meniscal lesion includes conservative, as well as operative, procedures. The goals of surgery are to reduce pain and disability, as well as to preserve meniscal function without causing additional cartilage damage. The resection of meniscal tissue should be restricted to as much as is necessary, and as little as is reasonably possible. Postoperative rehabilitation serves the purpose of improving functional deficits and pain, as well as of restoring a good range of motion and preventing secondary damage. It is the surgical therapy that dictates the aftercare, and with regards to the latter, there are clear differences between meniscectomy and meniscal repair. Keywords: meniscectomy, osteoarthritis, meniscus pathology, meniscus function

Rotated Hough filtering for automatically distinguishing the collagen bundles in the most superficial layer of articular cartilage.

The structure of the collagen matrix in the most superficial layer of articular cartilage (AC) is particularly critical to the wear and tensile resistance of AC. Disruption of the collagen network leads to rapid wear of the articular surface, which is a major contributory factor of osteoarthritis. Interwoven fiber bundles have been observed in the most superficial layer of healthy AC under confocal microscopy, but gradually disappear with age and pathological change of AC. The image analysis techniques developed in this paper aimed to provide a quantitative description of the relationship between the presence of the fiber bundles in the lamina splendens and health status of AC. The result of this quantitative study confirmed the existence of fiber bundles in healthy AC, and the accuracy of the identified fiber bundles was up to 90%. With the development of confocal arthroscopy for imaging microstructure of AC without biopsy, the image analysis technique can aid to efficiently assess the physiological status of AC for orthopedic clinics.

Wnt Inhibitory Factor 1 Deficiency Uncouples Cartilage and Bone Destruction in Tumor Necrosis Factor α–Mediated Experimental Arthritis

Wnt signaling plays a pivotal role in skeletal development and in the control of cartilage and bone turnover. We have recently shown that the secreted Wnt antagonist Wnt inhibitory factor 1 (WIF-1) is mainly expressed in the upper layers of epiphyseal and articular cartilage and, to a lesser extent, in bone. Nevertheless, WIF-1(-/-) mice develop normally. In light of these findings, we undertook this study to analyze the role of WIF-1 in arthritis. Expression analyses for WIF-1 were performed by real-time reverse transcription-polymerase chain reaction (RT-PCR). WIF-1(-/-) and tumor necrosis factor (TNF)-transgenic mice were crossbred, and the progression of arthritis in TNF-transgenic WIF-1(-/-) mice and littermate controls was evaluated. Structural joint damage was analyzed by histologic staining, histomorphometry, and micro-computed tomography. Wnt/β-catenin signaling was investigated by real-time RT-PCR and immunofluorescence on primary chondrocytes. WIF-1 expression was repressed by TNFα in chondrocytes and osteoblasts and down-regulated in experimental arthritis and in articular cartilage from patients with rheumatoid arthritis. WIF-1 deficiency partially protected TNF-transgenic mice against bone erosion and loss of trabecular bone, probably as a result of less osteoclast activity. In contrast, arthritis-related cartilage damage was aggravated by WIF-1 deficiency, while overexpression of WIF-1 attenuated cartilage degradation in TNF-transgenic mice. In chondrocytes, TNFα stimulated canonical Wnt signaling, which could be blocked by WIF-1, indicating a direct effect of TNFα and WIF-1 on Wnt signaling in this system. These data suggest that WIF-1 may take part in the fine-tuning of cartilage and bone turnover, promoting the balance of cartilage versus bone anabolism.