Covariance in human limb joint articular morphology

Objectives

Limb synovial joints exhibit complex shapes that must accommodate often-antagonistic demands of function, mobility, and stability. These demands presumably dictate coordination among joint articular shapes, but the structure of morphological covariance within and among joints is unknown. This study analyzes the human shoulder, elbow, hip, and knee to determine how articular covariance is structured in relation to joint structure, accessory cartilage, and function.

Materials and Methods

Surface models were created from the CT scans of 200 modern skeletons from the University of Tennessee Donated Skeletal Collection. Three-dimensional landmarks were collected on the shoulder, elbow, hip, and knee joints. Two-block partial least squares were conducted to determine associations between surfaces of conarticular shapes, functionally analogous articulations, and articulations belonging to the same bone.

Results

Except for the components of the shoulder, all conarticular pairs exhibit covariance, though the strength of these relationships appears unrelated to the amount of accessory cartilage in the joint. Only the analogous articulations of the humerus and femur exhibit significant covariance, but it is unlikely that this pattern is due to function alone. Stronger covariance within the lower limb than the upper limb is consistent broader primate patterns of within-limb integration.

Discussion

With the exception of the elbow, complementary joint function does not appear to promote strong covariance between articulations. Analogous humeral and femoral surfaces are also serially homologous, which may result in the articular associations observed between these bones. Broadly, these patterns highlight the indirect relationship between joint congruence and covariance.

     

Structural and functional changes of the articular surface in a post-traumatic model of early osteoarthritis measured by atomic force microscopy

The functional integrity of the articulating cartilage surface is a critical determinant of joint health. Although a variety of techniques exist to characterize the structural changes in the tissue with osteoarthritis (OA), some with extremely high resolution, most lack the ability to detect and monitor the functional changes that accompany the structural deterioration of this essential bearing surface. Atomic force microscopy (AFM) enables the acquisition of both structural and mechanical properties of the articular cartilage surface, with up to nanoscale resolution, making it particularly useful for evaluating the functional behavior of the macromolecular network forming the cartilage surface, which disintegrates in OA.In the present study, AFM was applied to the articular cartilage surfaces from six pairs of canine knee joints with post-traumatic OA. Microstructure (RMS roughness) and micromechanics (dynamic indentation modulus, E^?) of medial femoral condyle cartilages were compared between contralateral controls and cruciate-transected knee joints, which develop early signs of OA by three months after surgery.Results reveal a significant increase in RMS roughness and a significant four-fold decrease in E^? in cartilages from cruciate-transected joints versus contralateral controls. Compared to previous reports of changes in bulk mechanics, AFM was considerably more sensitive at detecting early cartilage changes due to cruciate-deficiency. The use of AFM in this study provides important new information on early changes in the natural history of OA because of its ability to sensitively detect and measure local structural and functional changes of the articular cartilage surface, the presumptive site of osteoarthritic initiation.     

Congruency Effects on Load Bearing in Diarthrodial Joints

Modelling load bearing in diarthrodial joints is challenging, due to the complexity of the materials, the boundary and interface conditions and the geometry. The articulating surfaces are covered with cartilage layers that are filled with a fluid that plays a major role in load bearing [Mow, V.C., Holmes, M.H., Lai, W.M. (1984) “Survey article: fluid transport and mechanical properties of articular cartilage: a review”, Journal of Biomechanics 17(5), 377–394]. Researchers have tended to approximate joint geometry using axisymmetry [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) “Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure”, Journal of Biomechanics 32, 1037–1047], often with a rounded upper articulating surface, creating a form of Hertz problem [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) “Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure”, Journal of Biomechanics 32, 1037–1047]. However, diarthrodial joints (shoulder, hip and knee) are equipped with peripheral structures (glenoid labrum, acetabular labrum and meniscus, respectively) that tend to deepen the joint contact and thus cause initial contact to be established at the periphery of the joint rather than “centrally”. The surface geometries are purposefully incongruent, and the incongruency has a significant effect on the stresses, pressures and pressure gradients inside the tissue. The models show the importance of the peripheral structures and the incongruency from a load-bearing perspective. Joint shapes must provide a compromise between demands for load-bearing, lubrication and the supply of nutrients to the chondrocytes of the cartilage and cells of the peripheral structures. Retention and repair of the functionality of these peripheral structures should be a prime consideration in any surgical treatment of an injured joint.     

Experimental evaluation of current and novel approximations of articular surfaces of the ankle joint

Kinematics and flexibility properties of both natural and replaced ankle joints are affected by the geometry of the articulating surfaces. Recent studies proposed an original saddle-shaped, skewed, truncated cone with laterally oriented apex, as tibiotalar contact surfaces for ankle prosthesis. The goal of this study was to compare in vitro this novel design with traditional cylindrical or medially centered conic geometries in terms of their ability to replicate the natural ankle joint mechanics. Ten lower limb cadaver specimens underwent a validated process of custom design for the replacement of the natural ankle joint. The process included medical imaging, 3D modeling and printing of implantable sets of artificial articular surfaces based on these three geometries. Kinematics and flexibility of the overall ankle complex, along with the separate ankle and subtalar joints, were measured under cyclic loading. In the neutral and in maximum plantarflexion positions, the range of motion under torques in the three anatomical planes of the three custom artificial surfaces was not significantly different from that of the natural surfaces. In maximum dorsiflexion the difference was significant for all three artificial surfaces at the ankle complex, and only for the cylindrical and medially centered conic geometries at the tibiotalar joint. Natural joint flexibility was restored by the artificial surfaces nearly in all positions. The present study provides experimental support for designing articular surfaces matching the specific morphology of the ankle to be replace, and lays the foundations of the overall process for designing and manufacturing patient-specific total ankle replacements.     

Postnatal development of collagen structure in ovine articular cartilage

Background  

Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly parallel to the articular surface near the articular surface. Recent studies into collagen fibre orientation in stillborn and juvenile animals showed that this structure is absent at birth. Since the collagen structure is an important factor for AC mechanics, the absence of the adult Benninghoff structure has implications for perinatal AC mechanobiology. The current objective is to quantify the dynamics of collagen network development in a model animal from birth to maturity. We further aim to show the presence or absence of zonal differentiation at birth, and to assess differences in collagen network development between different anatomical sites of a single joint surface. We use quantitative polarised light microscopy to investigate properties of the collagen network and we use the sheep (Ovis aries) as our model animal.     

Identification of intra-group,inter-individual,and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane

Introduction  

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease characterized by overexpression of pro-inflammatory/pro-destructive genes and other activating genes (for example, proto-oncogenes) in the synovial membrane (SM). The gene expression in disease is often characterized by significant inter-individual variances via specific synchronization/desynchronization of gene expression. To elucidate the contribution of the variance to the pathogenesis of disease, expression variances were tested in SM samples of RA patients, osteoarthritis (OA) patients, and normal controls (NCs).     

Exosomes from IL-1β stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes

Introduction

Osteoarthritis (OA) is a whole joint disease, and characterized by progressive degradation of articular cartilage, synovial hyperplasia, bone remodeling and angiogenesis in various joint tissues. Exosomes are a type of microvesicles (MVs) that may play a role in tissue-tissue and cell-cell communication in homeostasis and diseases. We hypothesized that exosomes function in a novel regulatory network that contributes to OA pathogenesis and examined the function of exosomes in communication among joint tissue cells.

Methods

Human synovial fibroblasts (SFB) and articular chondrocytes were obtained from normal knee joints. Exosomes isolated from conditioned medium of SFB were analyzed for size, numbers, markers and function. Normal articular chondrocytes were treated with exosomes from SFB, and Interleukin-1β (IL-1β) stimulated SFB. OA-related genes expression was quantified using real-time PCR. To analyze exosome effects on cartilage tissue, we performed glycosaminoglycan release assay. Angiogenic activity of these exosomes was tested in migration and tube formation assays. Cytokines and miRNAs in exosomes were analyzed by Bio-Plex multiplex assay and NanoString analysis.

Results

Exosomes from IL-1β stimulated SFB significantly up-regulated MMP-13 and ADAMTS-5 expression in articular chondrocytes, and down-regulated COL2A1 and ACAN compared with SFB derived exosomes. Migration and tube formation activity were significantly higher in human umbilical vein endothelial cells (HUVECs) treated with the exosomes from IL-1β stimulated SFB, which also induced significantly more proteoglycan release from cartilage explants. Inflammatory cytokines, IL-6, MMP-3 and VEGF in exosomes were only detectable at low level. IL-1β, TNFα MMP-9 and MMP-13 were not detectable in exosomes. NanoString analysis showed that levels of 50 miRNAs were differentially expressed in exosomes from IL-1β stimulated SFB compared to non-stimulated SFB.

Conclusions

Exosomes from IL-1β stimulated SFB induce OA-like changes both in vitro and in ex vivo models. Exosomes represent a novel mechanism by which pathogenic signals are communicated among different cell types in OA-affected joints.     

Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome

Introduction

Arthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, detailed information on arthritis in Blau syndrome on which the therapeutic strategy should be based on is lacking. This multi-center study aimed to accurately characterize the articular manifestation of Blau syndrome and also to demonstrate the utility of musculoskeletal ultrasound in Blau syndrome.

Methods

Patients who had been diagnosed with Blau syndrome by genetic analysis of NOD2 were recruited. A total of 102 synovial sites in 40 joints were assessed semiquantitatively by ultrasound for gray-scale synovitis and synovial power Doppler (PD) signal.

Results

In total, 10 patients whose age ranged from 10 months to 37 years enrolled in this study. Although only 4 joints (0.8%) were tender on physical examination, 81 joints (16.9%) were clinically swollen. Moreover, 240 (50.0%), and 124 (25.8%) joints showed gray-scale (GS) synovitis and synovial PD signal on ultrasound, respectively. Importantly, GS synovitis was present in 168 out of 399 non-swollen joints, in which 61 also exhibited synovial PD signal. Among 40 joint regions, the ankle, the wrist, and the proximal interphalangeal joints were the most frequently and severely affected joints. Comparisons between different synovial tissues demonstrated a significantly higher proportion of the joints with tenosynovitis as compared with that with intra-articular synovitis (41.5% versus 27.9%, P < 0.0001). In respect of age and treatment, synovial PD signals were minimal in the youngest patient and in the oldest two patients, and were relatively mild in patients receiving treatment with methotrexate plus TNF antagonists. In two patients who underwent the second ultrasound examination, total PD scores markedly decreased after initiating the treatment with a tumor necrosis factor (TNF) antagonist.

Conclusions

The detailed information on synovial inflammation obtained by ultrasound confirms the dissociation between pain and inflammation and the frequently involved joint regions and synovial tissue in the arthritis of Blau syndrome. Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition.     

Cross-Talk Correction Method for Knee Kinematics in Gait Analysis Using Principal Component Analysis (PCA): A New Proposal

Background

In 3D gait analysis, the knee joint is usually described by the Eulerian way. It consists in breaking down the motion between the articulating bones of the knee into three rotations around three axes: flexion/extension, abduction/adduction and internal/external rotation. However, the definition of these axes is prone to error, such as the “cross-talk” effect, due to difficult positioning of anatomical landmarks. This paper proposes a correction method, principal component analysis (PCA), based on an objective kinematic criterion for standardization, in order to improve knee joint kinematic analysis.

Methods

The method was applied to the 3D gait data of two different groups (twenty healthy subjects and four with knee osteoarthritis). Then, this method was evaluated with respect to three main criteria: (1) the deletion of knee joint angle cross-talk (2) the reduction of variance in the varus/valgus kinematic profile (3) the posture trial varus/valgus deformation matching the X-ray value for patients with knee osteoarthritis. The effect of the correction method was tested statistically on variabilities and cross-talk during gait.

Results

Cross-talk was lower (p<0.05) after correction (the correlation between the flexion-extension and varus-valgus kinematic profiles being annihilated). Additionally, the variance in the kinematic profile for knee varus/valgus and knee flexion/extension was found to be lower and higher (p<0.05), respectively, after correction for both the left and right side. Moreover, after correction, the posture trial varus/valgus angles were much closer to x-ray grading.

Conclusion

The results show that the PCA correction applied to the knee joint eliminates the cross-talk effect, and does not alter the radiological varus/valgus deformation for patients with knee osteoarthritis. These findings suggest that the proposed correction method produces new rotational axes that better fit true knee motion.     

Unveiling the environmental drivers of intraspecific body size variation in terrestrial vertebrates

Aim

Whether intraspecific spatial patterns in body size are generalizable across species remains contentious, as well as the mechanisms underlying these patterns. Here we test several hypotheses explaining within-species body size variation in terrestrial vertebrates including the heat balance, seasonality, resource availability and water conservation hypotheses for ectotherms, and the heat conservation, heat dissipation, starvation resistance and resource availability hypotheses for endotherms.

Location

Global.

Time period

1970–2016.

Major taxa studied

Amphibians, reptiles, birds and mammals.

Methods

We collected 235,905 body size records for 2,229 species (amphibians = 36; reptiles = 81; birds = 1,545; mammals = 567) and performed a phylogenetic meta-analysis of intraspecific correlations between body size and environmental variables. We further tested whether correlations differ between migratory and non-migratory bird and mammal species, and between thermoregulating and thermoconforming ectotherms.

Results

For bird species, smaller intraspecific body size was associated with higher mean and maximum temperatures and lower resource seasonality. Size–environment relationships followed a similar pattern in resident and migratory birds, but the effect of resource availability on body size was slightly positive only for non-migratory birds. For mammals, we found that intraspecific body size was smaller with lower resource availability and seasonality, with this pattern being more evident in sedentary than migratory species. No clear size–environment relationships were found for reptiles and amphibians.

Main conclusions

Within-species body size variation across endotherms is explained by disparate underlying mechanisms for birds and mammals. Heat conservation (Bergmann's rule) and heat dissipation are the dominant processes explaining biogeographic intraspecific body size variation in birds, whereas in mammals, body size clines are mostly explained by the starvation resistance and resource availability hypotheses. Our findings contribute to a better understanding of the mechanisms behind species adaptations to the environment across their geographic distributions.     

Ultrasonographic Features of Hip Joints in Mucopolysaccharidoses Type I and II

Objectives

The primary aim of this study was to assess the ultrasonographic features of hip joints in patients with mucopolysaccharidosis (MPS) type I and II in comparison with healthy population. The secondary aims were to correlate these features with clinical measures and to evaluate the utility of ultrasound in the diagnosis of MPS disease.

Materials and Methods

Sixteen MPS I (n = 3) and II (n = 13) patients were enrolled in the present study and underwent clinical and radiological evaluation, and bilateral high-resolution ultrasonography (US) of hip joints. The distance from the femoral neck to joint capsule (synovial joint space, SJS), joint effusion, synovial hyperthrophy, and local pathological vascularization were evaluated. The results were compared to the healthy population and correlated with clinical and radiological measures.

Results

1. There was a difference in US SJS between children with MPS disease and the normative value for healthy population (7mm). Mean values of SJS were 15.81 ± 4.08 cm (right hip joints) and 15.69 ± 4.19 cm (left joints). 2. No inflammatory joint abnormalities were detected in MPS patients. 3. There was a clear correlation between US SJS and patients’ age and height, while no clear correlation was observed between SJS and disease severity.

Conclusions

1. Patients with MPS I and II present specific features in hip joint ultrasonography. 2. The data suggests that ultrasonography might be effective in the evaluation of hip joint involvement in patients with MPS and might present a valuable tool in facilitating the diagnosis and follow up of the disease.     

Rapid prototyping of anatomically shaped, tissue-engineered implants for restoring congruent articulating surfaces in small joints

Background:  Preliminary studies investigated advanced scaffold design and tissue engineering approaches towards restoring congruent articulating surfaces in small joints.
Materials and methods:  Anatomical femoral and tibial cartilage constructs, fabricated by three-dimensional fibre deposition (3DF) or compression moulding/particulate leaching (CM), were evaluated in vitro and in vivo in an autologous rabbit model. Effects of scaffold pore architecture on rabbit chondrocyte differentiation and mechanical properties were evaluated following in vitro culture and subcutaneous implantation in nude mice. After femoral and tibial osteotomy and autologous implantation of tissue-engineered constructs in rabbit knee joints, implant fixation and joint articulation were evaluated.
Results:  Rapid prototyping of 3DF architectures with 100% interconnecting pores promoted homogeneous distribution of viable cells, glycosaminoglycan (GAG) and collagen type II; significantly greater GAG content and differentiation capacity (GAG/DNA) in vitro compared to CM architectures; and higher mechanical equilibrium modulus and dynamic stiffness (at 0.1 Hz). Six weeks after implantation, femoral and tibial constructs had integrated with rabbit bone and knee flexion/extension and partial load bearing were regained. Histology demonstrated articulating surfaces between femoral and tibial constructs for CM and 3DF architectures; however, repair tissue appeared fibrocartilage-like and did not resemble implanted cartilage.
Conclusions:  Anatomically shaped, tissue-engineered constructs with designed mechanical properties and internal pore architectures may offer alternatives for reconstruction or restoration of congruent articulating surfaces in small joints.     

Contribution of genetic effects to genetic variance components with epistasis and linkage disequilibrium

Background

Cockerham genetic models are commonly used in quantitative trait loci (QTL) analysis with a special feature of partitioning genotypic variances into various genetic variance components, while the F_∞ genetic models are widely used in genetic association studies. Over years, there have been some confusion about the relationship between these two type of models. A link between the additive, dominance and epistatic effects in an F_∞ model and the additive, dominance and epistatic variance components in a Cockerham model has not been well established, especially when there are multiple QTL in presence of epistasis and linkage disequilibrium (LD).

Results

In this paper, we further explore the differences and links between the F_∞ and Cockerham models. First, we show that the Cockerham type models are allelic based models with a special modification to correct a confounding problem. Several important moment functions, which are useful for partition of variance components in Cockerham models, are also derived. Next, we discuss properties of the F_∞ models in partition of genotypic variances. Its difference from that of the Cockerham models is addressed. Finally, for a two-locus biallelic QTL model with epistasis and LD between the loci, we present detailed formulas for calculation of the genetic variance components in terms of the additive, dominant and epistatic effects in an F_∞ model. A new way of linking the Cockerham and F_∞ model parameters through their coding variables of genotypes is also proposed, which is especially useful when reduced F_∞ models are applied.

Conclusion

The Cockerham type models are allele-based models with a focus on partition of genotypic variances into various genetic variance components, which are contributed by allelic effects and their interactions. By contrast, the F_∞ regression models are genotype-based models focusing on modeling and testing of within-locus genotypic effects and locus-by-locus genotypic interactions. When there is no need to distinguish the paternal and maternal allelic effects, these two types of models are transferable. Transformation between an F_∞ model's parameters and its corresponding Cockerham model's parameters can be established through a relationship between their coding variables of genotypes. Genetic variance components in terms of the additive, dominance and epistatic genetic effects in an F_∞ model can then be calculated by translating formulas derived for the Cockerham models.

     

Quantitative detection of cartilage surfaces and ligament geometry of the wrist using an imaging cryomicrotome system

Biomechanical models may aid in improving diagnosis and treatment of wrist joint disorders. As input, geometrical information is required for model development. Previous studies acquired some elements of the average wrist joint geometry. However, there is a close geometric functional match between articulating surfaces and ligament geometry. Therefore, biomechanical models need to be fed with the geometric data of individual joints. This study is aimed at acquiring geometric data of cartilage surfaces and ligaments from individual wrist joints by using a cryomicrotome imaging system and the evaluation of inter- and intra-observer variability of the data.The 3D geometry of 30 cartilage surfaces and 15 ligaments in three cadaver wrists was manually detected and quantitatively reconstructed. The inter- and intra-observer variability of the cartilage surface detection was 0.14 and 0.19 mm, respectively. For the position of the radius attachment of the dorsal radiocarpal ligament (DRC), the observer variations were 0.12 and 0.65 mm, for intra-/inter-observer, respectively. For the DRC attachment on the triquetrum, the observer variations were 0.22 and 1.19 mm.Anatomic reconstruction from 3D cryomicrotome images offer a method to obtain unique geometry data of the entire wrist joint for modeling purposes.     

Comparison of nonlinear mechanical properties of bovine articular cartilage and meniscus

Nonlinear, linear and failure properties of articular cartilage and meniscus in opposing contact surfaces are poorly known in tension. Relationships between the tensile properties of articular cartilage and meniscus in contact with each other within knee joints are also not known. In the present study, rectangular samples were prepared from the superficial lateral femoral condyle cartilage and lateral meniscus of bovine knee joints. Tensile tests were carried out with a loading rate of 5 mm/min until the tissue rupture. Nonlinear properties of the toe region, linear properties in larger strains, and failure properties of both tissues were analysed. The strain-dependent tensile modulus of the toe region, Young's modulus of the linear region, ultimate tensile stress and toughness were on average 98.2, 8.3, 4.0 and 1.9 times greater (p<0.05) for meniscus than for articular cartilage. In contrast, the toe region strain, yield strain and failure strain were on average 9.4, 3.1 and 2.3 times greater (p<0.05) for cartilage than for meniscus. There was a significant negative correlation between the strain-dependent tensile moduli of meniscus and articular cartilage samples within the same joints (r=−0.690, p=0.014). In conclusion, the meniscus possesses higher nonlinear and linear elastic stiffness and energy absorption capability before rupture than contacting articular cartilage, while cartilage has longer nonlinear region and can withstand greater strains before failure. These findings point out different load carrying demands that both articular cartilage and meniscus have to fulfil during normal physiological loading activities of knee joints.     

Osteopontin Level in Synovial Fluid Is Associated with the Severity of Joint Pain and Cartilage Degradation after Anterior Cruciate Ligament Rupture

Objective

To explore the molecular function of Osteopontin (OPN) in the pathogenesis of human OA, we compared the expression levels of OPN in synovial fluid with clinical parameters such as arthroscopic observation of cartilage damage and joint pain after joint injury.

Methods

Synovial fluid was obtained from patients who underwent anterior cruciate ligament (ACL) reconstruction surgery from 2009 through 2011 in our university hospital. The amounts of intact OPN (OPN Full) and it’s N-terminal fragment (OPN N-half) in synovial fluid from each patient were quantified by ELISA and compared with clinical parameters such as severity of articular cartilage damage (TMDU cartilage score) and severity of joint pain (Visual Analogue Scale and Lysholm score).

Results

Within a month after ACL rupture, both OPN Full and N-half levels in patient synovial fluid were positively correlated with the severity of joint pain. In contrast, patients with ACL injuries greater than one month ago felt less pain if they had higher amounts of OPN N-half in synovial fluid. OPN Full levels were positively correlated with articular cartilage damage in lateral tibial plateau.

Conclusion

Our data suggest that OPN Full and N-half have distinct functions in articular cartilage homeostasis and in human joint pain.     

Degeneration of normal articular cartilage induced by late phase osteoarthritic synovial fluid in beagle dogs

Objective

To investigate the pathogenesis of late phase osteoarthritic (OA) synovial fluid (SF) on normal articular cartilage in vivo and provide an understanding of degenerative cartilage extending in OA joint.

Methods

A random knee, each of 8 beagle dogs, received anterior cruciate ligament transection (ACLT) and was confirmed to have late phase OA degenerative changes at 24 weeks after operation. Thereafter, one random elbow of each canine was injected with autologous late phase OA knee SF. The contralateral elbow was injected with normal saline (NS) of the same volume as SF aspirated from ACLT knee. These two groups of elbows were labeled “SF” and “NS”. 8 other beagle dogs were left intact and placed in Group Control. After aseptic arthrocentesis was performed weekly on both elbows for 24 weeks, morphological changes were observed in the cartilage of the elbows, and expressions of 7 biological etiological factors of chondrocytes of the elbows were determined in Group SF, Group NS and Group Control, respectively.

Results

Morphological changes were observed in articular cartilage of the elbows in Group SF. Levels of unit area of collagen type I in the noncalcified, calcified and full zones of articular cartilage of the elbows in Group SF increased significantly. Level of unit area of collagen type III in the calcified zone of articular cartilage of the elbows in Group SF remained unchanged. Meanwhile, expressions of MMP-1 and MMP-3 of chondrocytes of the elbows in Group SF increased significantly. There was almost no difference between articular cartilage in Group NS and Group Control.

Conclusion

Based on these results, we conclude that OA degeneration of normal articular cartilage can be independently induced by late phase OA SF. Endogenous OA biological etiological factor may be one of the reasons causing degenerative cartilage extending in OA joint.     

Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis

Introduction

Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee.

Methods

Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid.

Results

Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues.

Conclusion

These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA.     

Chondrocalcinosis is common in the absence of knee involvement

Introduction

We aimed to describe the distribution of radiographic chondrocalcinosis (CC) and to examine whether metacarpophalangeal joint (MCPJ) calcification and CC at other joints occurs in the absence of knee involvement.

Methods

This was a cross-sectional study embedded in the Genetics of Osteoarthritis and Lifestyle study (GOAL). All participants (n = 3,170) had radiographs of the knees, hands, and pelvis. These were scored for radiographic changes of osteoarthritis (OA), for CC at knees, hips, symphysis pubis, and wrists, and for MCPJ calcification. The prevalence of MCPJ calcification and CC overall, at each joint, and in the presence or absence of knee involvement, was calculated.

Results

The knee was the commonest site of CC, followed by wrists, hips, and symphysis pubis. CC was more likely to be bilateral at knees and wrists but unilateral at hips. MCPJ calcification was usually bilateral, and less common than CC at knees, hips, wrists, and symphysis pubis. Unlike that previously reported, CC commonly occurred without any knee involvement; 44.4% of wrist CC, 45.9% of hip CC, 45.5% of symphysis pubis CC, and 31.3% of MCPJ calcification occurred in patients without knee CC. Those with meniscal or hyaline articular cartilage CC had comparable ages (P = 0.21), and neither preferentially associated with fibrocartilage CC at distant joints.

Conclusions

CC visualized on a plain radiograph commonly occurs at other joints in the absence of radiographic knee CC. Therefore, knee radiographs alone are an insufficient screening test for CC. This has significant implications for clinical practice, for epidemiologic and genetic studies of CC, and for the definition of OA patients with coexistent crystal deposition.