Spinal arthritis and physical stress at Bronze Age Harappa

This study examines joint changes in the vertebral skeleton in human remains excavated in 1987 and 1988 at Bronze Age Harappa, an urban center of the Indus Valley civilization. The sample consists of 23 complete skeletons from primary burial context, the partial remains of more than 69 other individuals, and hundreds of skeletal elements from secondary context, totalling 3,084 vertebral joint margins and articular surfaces. Marginal bone proliferation, pitting of articular surfaces, eburnation, and ankylosis were scored macroscopically for vertebral body margins and surfaces and posterior apophyseal facet joints. Marginal lipping is far more prevalent on the vertebral bodies than on the apophyseal facets and surface pitting is also more frequent on vertebral bodies although its expression is relatively low overall. Cervical vertebrae in this sample exhibit the same amount of marginal new bone and much more surface pitting of the vertebral bodies than do either thoracic or lumbar vertebrae; the cervical segment also exhibits the most severe expressions of both types of lesions. In addition, although the frequencies of cervical and lumbar posterior facet involvement are similar, the cervical facets exhibit much more severe lipping as well as the only cases of eburnation and ankylosis. Pitting of the posterior facets is most common in the lumbar segment, but the cervical examples are the only severe cases. It is proposed that the severe joint changes in the cervical spine result from trauma, perhaps accumulated microtrauma from activity stresses. There are no age or sex associated patterns in the frequency of arthritis although this result may be influenced by the small proportions of the total sample for which age and sex could be determined. © 1994 Wiley-Liss, Inc.     

Sex differences in activity-related osseous change in the spine and the gendered division of labor at Ensay and Wharram Percy, UK

Sex differences in the distribution of vertebral degenerative and plastic change were examined and compared within and between samples of 51 individuals from the historically and ethnographically documented 16th-19th century site of Ensay, the Outer Hebrides, and 59 individuals from the medieval site of Wharram Percy, the Yorkshire Wolds. Both populations have a known gendered division of labor between males and females and known activity-related stresses on the spine. Osseous changes normally associated with degenerative joint disease (osteoarthritis) of the apophyseal facets and osteophytosis of the vertebral bodies were scored and reported separately. Inter- and intrasite differences were found in the frequency and distribution of osseous change down the spine. Overall, the Ensay sample was more highly stressed than that from Wharram Percy. Furthermore, differences between males and females at Ensay could be identified as relating to different types of activities. Distinctions between males and females at Wharram Percy were less marked, suggesting broadly similar lifestyles. These results accorded with expectations regarding contrasting levels of activity-related stress at the two sites and the division of labor between males and females. In particular, the prevalence and distribution of facet remodeling, facet sclerosis/eburnation, and osteophytosis in Ensay females could be related to load-bearing using creels (a form of basket), which disrupted "normal" patterns of osseous change along the spine. Importantly, morphologically distinct osseous modifications recorded on the apophyseal facets produced dissimilar distributions, suggesting that they may have different etiologies. These results highlight the need for a high degree of discrimination in recording, analyzing, and exploring activity-related osseous change.     

Vertebral arthritis and physical activities in the prehistoric Southeastern United States

Vertebral arthritis is examined in a prehistoric Native American sample from northwestern Alabama. Both osteophytosis (OP) of the vertebral bodies and osteoarthritis (OA) of the apophyseal facets are highest in the lumbar vertebrae, followed by the cervical and thoracic segments, although differences are much more striking in OP. OA is bilaterally asymmetric, with greater prevalence on the right side in the upper thoracic region. Much of the patterning seen in arthritis in this and other samples is due to the stresses imposed by spinal curvature and weight-bearing due to our erect posture. In addition, handedness is the probable cause of asymmetry in OA. However, the high levels of cervical OP are unexpected, and may be due to use of the tumpline in carrying burdens. © 1994 Wiley-Liss, Inc.     

Measuring and interpreting age‐related loss of vertebral bone mineral density in a medieval population

This study investigates the age‐ and sex‐related patterns in vertebral bone mineral density (BMD) and the relationship between BMD and vertebral osteophytosis (VO), using a specialized peripheral densitometer in a skeletal sample excavated from the British medieval village Wharram Percy. A total of 58 individuals were divided by sex into three broad age categories (18–29, 30–49, 50+ years.). Each fourth intact vertebral centra was scored for VO and 5‐mm thick coronal sections scanned in a specialized peripheral densitometer (GE Lunar Piximus DXA). Changes in BMD associated with age, sex, and VO severity were examined in the whole vertebral section, a strictly trabecular region, and a primarily cortical region of bone separately. Significant change in vertebral BMD was found to occur by middle age with little or no statistical change in BMD between middle and old age. Females appear to suffer greater bone loss at an earlier age with no change in BMD between middle and old age, whereas males show a more steady loss of BMD across the age groups. The bone mineral content and BMD of the cortical region is higher in individuals with pronounced/severe osteophytosis. The unusual age‐ and sex‐related patterns of change in vertebral BMD at Wharram Percy are compared with the patterns of age‐related change from recent longitudinal population‐based studies. The results emphasize the different pattern of bone loss in young adulthood seen in trabecular regions of the skeleton and highlight the importance of consideration of degenerative joint disease in BMD studies. The influence of lifestyle factors on vertebral BMD in this medieval population is also discussed. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.     

Life stress on the Roman limes in continental Croatia

The purpose of the paper is to analyze and compare the demographic profiles and disease frequencies between a skeletal series from Zmajevac, a settlement on the Danubian limes, and a composite «non-limes» skeletal series consisting of human osteological remains from three large urban settlements to the west of the limes; roman Mursa (modern Osijek), Cibalae (Vinkovci) and Certissia (Štrbinci). To determine if life stresses were different in settlements on the limes the age and sex distribution in Zmajevac was compared to the composite «non-limes» series. All skeletons were also analyzed for the presence of dental pathology, dental enamel hypoplasia, cribra orbitalia, trauma, and physical stress.

Data collected from the skeletal series show that, with the exception of some indicators of physical stress, no significant differences in quality of life is evident. Both series are characterized by an underrepresentation of subadults from the youngest age category and by similar average adult male and female ages at death. In Zmajevac the average ages at death for adult males and females were 40.0 and 39.0 years respectively, in the composite «non-limes» series 37.4 years for both males and females. The frequencies of dental disease, subadult stress indicators, and trauma are similar in both series. The only consistent difference between the two series is noted in the frequencies of skeletal markers of physical stress, in particular the frequencies of vertebral osteoarthritis and Schmorl's defects. Total male and total female vertebral osteoarthritis frequencies in the two series are significantly different, as is the difference in total male frequencies of Schmorl's defects. Young adult males in the Zmajevac series seem to have been experiencing particularly heavy physical strain on the vertebral column. They exhibit significantly higher frequencies of both vertebral osteoarthritis and Schmorl's defects than young adult males from the composite non-limes series.     

饲料中植物油替代鱼油对大西洋鲑肝细胞油酸跨膜吸收的影响

以 1-14C油酸（oleic acid;18:1n-9,OA）为指示剂,研究了不同饲料油源饲喂下大西洋鲑肝细胞膜脂肪酸组成受到改变时该细胞对OA吸收的状况,以探讨植物油（Vegetable oil,VO）替代鱼油（Fish oil,FO）对大西洋鲑肝细胞脂肪酸跨膜吸收的影响,为大西洋鲑饲料中植物油替代鱼油的可行性提供理论依据。试验先以鱼油和大豆油为油源配制两种全价配合饲料,分别饲喂大西洋鲑幼鲑5个月,使其产生不同的脂肪酸组成。在饲养结束后,分离并培养试验鱼肝细胞,将细胞与1-14COA及37.5 mol/L OA（1/30,mol/mol,0.3 Ci/瓶）共孵育2h,收集并测定细胞内OA放射活性,再计算细胞内OA吸收量 nmol/（hmillion cells）。同时,试验采取RT-PCR方法测定了细胞脂肪酸运送蛋白（Fatty acid transport protein,FATP）、脂肪酸移位蛋白（Fatty acid translocase,FAT/CD36）的基因表达量。结果表明,FO和VO组肝细胞对OA吸收分别为（0.9240.258）及（0.8880.179）nmol/（hmillion cells）,两组间无显著差异（P0.05）。RT-PCR的检测结果表明,FAT/CD36和FATP基因表达量在FO与VO两组间均无显著差异（P0.05）。结果表明,从植物油替代鱼油不影响大西洋鲑肝细胞对长链脂肪酸的跨膜吸收方面来看,大西洋鲑饲料中以植物油替代鱼油具有可行性。       

Protein modification by deamidation indicates variations in joint extracellular matrix turnover

As extracellular proteins age, they undergo and accumulate nonenzymatic post-translational modifications that cannot be repaired. We hypothesized that these could be used to systemically monitor loss of extracellular matrix due to chronic arthritic diseases such as osteoarthritis (OA). To test this, we predicted sites of deamidation in cartilage oligomeric matrix protein (COMP) and confirmed, by mass spectroscopy, the presence of deamidated (Asp(64)) and native (Asn(64)) COMP epitopes (mean 0.95% deamidated COMP (D-COMP) relative to native COMP) in cartilage. An Asp(64), D-COMP-specific ELISA was developed using a newly created monoclonal antibody 6-1A12. In a joint replacement study, serum D-COMP (p = 0.017), but not total COMP (p = 0.5), declined significantly after replacement demonstrating a joint tissue source for D-COMP. In analyses of 450 participants from the Johnston County Osteoarthritis Project controlled for age, gender, and race, D-COMP was associated with radiographic hip (p < 0.0001) but not knee (p = 0.95) OA severity. In contrast, total COMP was associated with radiographic knee (p < 0.0001) but not hip (p = 0.47) OA severity. D-COMP was higher in soluble proteins extracted from hip cartilage proximal to OA lesions compared with remote from lesions (p = 0.007) or lesional and remote OA knee (p < 0.01) cartilage. Total COMP in cartilage did not vary by joint site or proximity to the lesion. This study demonstrates the presence of D-COMP in articular cartilage and the systemic circulation, and to our knowledge, it is the first biomarker to show specificity for a particular joint site. We believe that enrichment of deamidated epitope in hip OA cartilage indicates a lesser repair response of hip OA compared with knee OA cartilage.     

Advanced Osteoarthritis in Humans Is Associated With Altered Collagen VI Expression and Upregulation of ER-stress Markers Grp78 and Bag-1

To test the hypothesis that a perturbation of endoplasmic reticulum (ER) function is involved in the pathogenesis of osteoarthritis (OA), articular cartilage was isolated from non-OA patients secondary to resection of osteo- or chondrosarcomas. Intra-joint samples of minimal and advanced osteoarthritic cartilage were isolated from patients undergoing total knee arthroplasty and scored for disease severity. Glucose-regulated protein-78 (grp78) and bcl-2–associated athanogene-1 (bag-1) were detected via immunofluorescence as markers of non-homeostatic ER function. Additionally, the expression of type VI collagen and its integrin receptor, NG2, was determined to examine cartilage matrix health and turnover. There was an upregulation of grp78 in advanced OA, and variable expression in minimal OA. Non-OA cartilage was consistently grp78 negative. The downstream regulator bag-1 was also upregulated in OA compared with normal cartilage. Collagen VI was mainly cell-associated in non-OA cartilage, with a more widespread distribution observed in OA cartilage along with increased intracellular staining intensity. The collagen VI integral membrane proteoglycan receptor NG2 was downregulated in advanced OA compared with its patient-matched minimally involved cartilage sample. These results suggest that chondrocytes exhibit ER stress during OA, in association with upregulation of a large secreted molecule, type VI collagen. (J Histochem Cytochem 57:923–931, 2009)     

Enzymatic activity and distribution of phospholipase A2 in human cartilage

Extracellular phospholipase A2 (PLA2) with proinflammatory activity has recently been discovered in synovial fluids in inflammatory arthritides. In the search for the sources of synovial fluid PLA2, human synovium and articular cartilage were found to contain large quantities of the enzyme. In rheumatoid arthritis (RA), PLA2 activity in synovium, superficial and deep layers of articular cartilage was 20 +/- 14 (SEM), 168 +/- 62 and 533 +/- 176 nmol/min/mg protein respectively. Corresponding values in osteoarthritis (OA) were 49 +/- 11, 569 +/- 109 and 1709 +/- 243 nmol/min/mg protein, all significantly higher (p less than .01) than in RA. Nasal septal cartilage contained much less PLA2, 19 +/- 5.6. PLA2 in human articular and nasal cartilage has sn-2 specificity, a neutral pH optimum and absolute calcium dependence. High PLA2 concentration in articular cartilage may imply that, at least in part, cartilage is the source of PLA2 in the joint space. Since RA cartilage and synovium have less PLA2 activity than the corresponding OA tissues, additional sources of PLA2 in RA synovial fluids are implicated.     

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.     

Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function

Oxidative stress leads to increased risk for osteoarthritis (OA) but the precise mechanism remains unclear. We undertook this study to clarify the impact of oxidative stress on the progression of OA from the viewpoint of oxygen free radical induced genomic instability, including telomere instability and resulting replicative senescence and dysfunction in human chondrocytes. Human chondrocytes and articular cartilage explants were isolated from knee joints of patients undergoing arthroplastic knee surgery for OA. Oxidative damage and antioxidative capacity in OA cartilage were investigated in donor-matched pairs of intact and degenerated regions of tissue isolated from the same cartilage explants. The results were histologically confirmed by immunohistochemistry for nitrotyrosine, which is considered to be a maker of oxidative damage. Under treatment with reactive oxygen species (ROS; 0.1 μmol/l H₂O₂) or an antioxidative agent (ascorbic acid: 100.0 μmol/l), cellular replicative potential, telomere instability and production of glycosaminoglycan (GAG) were assessed in cultured chondrocytes. In tissue cultures of articular cartilage explants, the presence of oxidative damage, chondrocyte telomere length and loss of GAG to the medium were analyzed in the presence or absence of ROS or ascorbic acid. Lower antioxidative capacity and stronger staining of nitrotyrosine were observed in the degenerating regions of OA cartilages as compared with the intact regions from same explants. Immunostaining for nitrotyrosine correlated with the severity of histological changes to OA cartilage, suggesting a correlation between oxidative damage and articular cartilage degeneration. During continuous culture of chondrocytes, telomere length, replicative capacity and GAG production were decreased by treatment with ROS. In contrast, treatment with an antioxidative agent resulted in a tendency to elongate telomere length and replicative lifespan in cultured chondrocytes. In tissue cultures of cartilage explants, nitrotyrosine staining, chondrocyte telomere length and GAG remaining in the cartilage tissue were lower in ROS-treated cartilages than in control groups, whereas the antioxidative agent treated group exhibited a tendency to maintain the chondrocyte telomere length and proteoglycan remaining in the cartilage explants, suggesting that oxidative stress induces chondrocyte telomere instability and catabolic changes in cartilage matrix structure and composition. Our findings clearly show that the presence of oxidative stress induces telomere genomic instability, replicative senescence and dysfunction of chondrocytes in OA cartilage, suggesting that oxidative stress, leading to chondrocyte senescence and cartilage ageing, might be responsible for the development of OA. New efforts to prevent the development and progression of OA may include strategies and interventions aimed at reducing oxidative damage in articular cartilage.     

Combined use of adipose derived stem cells and TGF-β3 microspheres promotes articular cartilage regeneration in vivo

We investigated enhancement of articular cartilage regeneration using a combination of human adipose derived stem cells (hADSCs) and TGF-β3 microspheres (MS) in vivo. Poly-lactic-co-glycolic acid (PLGA)MS were prepared using a solid/oil/water emulsion solvent evaporation-extraction method. The morphology of the MS was evaluated by scanning electron microscopy (SEM). The release characteristic of the TGF-β3 MS was evaluated. A New Zealand rabbit model for experimental osteoarthritis (OA) was established using the anterior medial meniscus excision method. Thirty OA rabbits were divided randomly into three groups according to different treatments of the right knee joints on day 7 after surgery: hADSCs/MS group received injection of both hADSCs and TGF-β3 MS; hADSCs group was injected with hADSCs; control group was injected with normal saline. Gross observation, histological staining and RT-PCR for collagen II and aggrecan) were used to assess the severity of OA and for evaluating the effect of combined use of hADSCs and TGF-β3 MS on articular cartilage regeneration in vivo. The MS were spherical with a smooth surface and the average diameter was 28 ± 2.3 µm. The encapsulation efficiency test showed that 73.8 ± 2.9% of TGF-β3 were encapsulated in the MS. The release of TGF- β3 lasted for at least 30 days. At both 6 and 12 weeks after injection, three groups exhibited different degrees of OA. Histological analysis showed that the hADSCs/MS group exhibited less OA than the hADSCs group, and the control group exhibited the most severe OA. Real-time RT-PCR showed that the gene expression of both collagen II and aggrecan were significantly up-regulated in the hADSCs/MS group. At 12 weeks after injection, the hADSCs/MS group also exhibited less OA than the other two groups. Combined use of hADSCs and TGF-β3 MS promoted articular cartilage regeneration in rabbit OA models.     

Functional morphology of the primate head and neck

The vertebral column plays a key role in maintaining posture, locomotion, and transmitting loads between body components. Cervical vertebrae act as a bridge between the torso and head and play a crucial role in the maintenance of head position and the visual field. Despite its importance in positional behaviors, the functional morphology of the cervical region remains poorly understood, particularly in comparison to the thoracic and lumbar sections of the spinal column. This study tests whether morphological variation in the primate cervical vertebrae correlates with differences in postural behavior. Phylogenetic generalized least-squares analyses were performed on a taxonomically broad sample of 26 extant primate taxa to test the link between vertebral morphology and posture. Kinematic data on primate head and neck postures were used instead of behavioral categories in an effort to provide a more direct analysis of our functional hypothesis. Results provide evidence for a function-form link between cervical vertebral shape and postural behaviors. Specifically, taxa with more pronograde heads and necks and less kyphotic orbits exhibit cervical vertebrae with longer spinous processes, indicating increased mechanical advantage for deep nuchal musculature, and craniocaudally longer vertebral bodies and more coronally oriented zygapophyseal articular facets, suggesting an emphasis on curve formation and maintenance within the cervical lordosis, coupled with a greater resistance to translation and ventral displacement. These results not only document support for functional relationships in cervical vertebrae features across a wide range of primate taxa, but highlight the utility of quantitative behavioral data in functional investigations. Am J Phys Anthropol 156:531–542, 2015. © 2015 Wiley Periodicals, Inc.     

Skeletal signs of activity in the Italian metal ages: Methodological and interpretative notes

In recent years anthropologists have made much progress in understanding ancient activities from skeletal remains. In this paper, material from the Iron Age cemetery at Pontecagnano (VII-IV century BC) is used to illustrate activity-related traits of eight basic categories:

The morphology of the thumb carpometacarpal joint does not differ between men and women,but changes with aging and early osteoarthritis

The high prevalence of thumb carpometacarpal (CMC) joint osteoarthritis (OA) in women has been previously linked to the articular morphology of the trapezium. Studies report conflicting results on how the articular shapes of male and female trapezia compare to one another, however, mainly because their findings are based on data from older cadaveric specimens. The purpose of this in vivo study was to dissociate the effect of sex from that of aging and early OA by using cohorts of healthy young and healthy older subjects, as well as patients with early stage OA. Computed tomography scans from 68 healthy subjects and 87 arthritic subjects were used to obtain 3-D bone models. The trapezial and metacarpal articular surfaces were manually delineated on scaled bone models and compared between sex, age, and health groups by using polar histograms of curvature and average curvatures. We found no sex-related differences, but significant age-group and health-group differences, in the articular surfaces of both bones. Older healthy subjects had higher curvature in the concave and lower curvature in the convex directions of both the trapezial and metacarpal saddles than healthy young subjects. Subjects with early OA had significantly different metacarpal and trapezial articular shapes from healthy subjects of the same age group. These findings suggest that aging and OA affect the articular shape of the CMC joint, but that, in contrast to previously held beliefs, inherent sex differences are not responsible for the higher incidence of CMC OA in women.     

Experimental analysis of the lower cervical spine in flexion with a focus on facet tracking

Cervical traumas are among the most common events leading to serious spinal cord injuries. While models are often used to better understand injury mechanisms, experimental data for their validation remain sparse, particularly regarding articular facets. The aim of this study was to assess the behavior of cervical FSUs under quasi-static flexion with a specific focus on facet tracking. 9 cadaveric cervical FSUs were imaged and loaded under a 10 Nm flexion moment, exerted incrementally, while biplanar X-rays were acquired at each load increment. The relative vertebral and facet rotations and displacements were assessed using radio-opaque markers implanted in each vertebra and CT-based reconstructions registered on the radiographs. The only failures obtained were due to specimen preparation, indicating a failure moment of cervical FSUs greater than 10 Nm in quasistatic flexion. Facet motions displayed a consistent anterior sliding and a variable pattern regarding their normal displacement. The present study offers insight on the behavior of cervical FSUs under quasi-static flexion beyond physiological thresholds with accurate facet tracking. The data provided should prove useful to further understand injury mechanisms and validate models.     

Post-traumatic osteoarthritis: the role of stress induced chondrocyte damage

Post-traumatic osteoarthritis is the form of osteoarthritis (OA) that develops following joint injury. Although its end-stage is indistinguishable from idiopathic OA, many patients with post-traumatic OA are younger than those with idiopathic OA, and they have a well-defined precipitating insult. Clinical and experimental studies suggest that excessive acute impact energy or chronic mechanical overload cause the degeneration of the articular surface responsible for post-traumatic OA. Yet, the mechanisms by which excessive mechanical force causes OA remain unknown. For these reasons it has not been possible to develop effective methods of preventing or decreasing the risk of post-traumatic OA. We hypothesized that mechanical loading that exceeds the tolerance of the articular surface causes chondrocyte damage due to oxidative stress. Our in vitro tests of human articular cartilage samples showed that shear stress causes chondrocyte death and that anti-oxidants decrease the shear stress induced cell death. These observations suggest that specific patterns of loading are particularly damaging to articular surfaces and that improved treatments of joint injuries may include mechanical methods of minimizing shear stresses and biologic methods of minimizing oxidative damage.     

Evidence of Spondyloarthropathy in the Spine of a Phytosaur (Reptilia: Archosauriformes) from the Late Triassic of Halberstadt,Germany

Pathologies in the skeleton of phytosaurs, extinct archosauriform reptiles restricted to the Late Triassic, have only been rarely described. The only known postcranial pathologies of a phytosaur are two pairs of fused vertebrae of “Angistorhinopsis ruetimeyeri” from Halberstadt, Germany, as initially described by the paleontologist Friedrich von Huene. These pathologic vertebrae are redescribed in more detail in this study in the light of modern paleopathologic methods. Four different pathologic observations can be made in the vertebral column of this individual: 1) fusion of two thoracic vertebral bodies by new bone formation within the synovial membrane and articular capsule of the intervertebral joint; 2) fusion and conspicuous antero-posterior shortening of last presacral and first sacral vertebral bodies; 3) destruction and erosion of the anterior articular surface of the last presacral vertebra; and 4) a smooth depression on the ventral surface of the fused last presacral and first sacral vertebral bodies. Observations 1–3 can most plausibly and parsimoniously be attributed to one disease: spondyloarthropathy, an aseptic inflammatory process in which affected vertebrae show typical types of reactive new bone formation and erosion of subchondral bone. The kind of vertebral shortening present in the fused lumbosacral vertebrae suggests that the phytosaur acquired this disease in its early life. Observation 4, the smooth ventral depression in the fused lumbosacral vertebrae, is most probably not connected to the spondyloarthropathy, and can be regarded as a separate abnormality. It remains of uncertain origin, but may be the result of pressure, perhaps caused by a benign mass such as an aneurysm or cyst of unknown type. Reports of spondyloarthropathy in Paleozoic and Mesozoic reptiles are still exceptional, and our report of spondyloarthropathy in fossil material from Halberstadt is the first unequivocal occurrence of this disease in a Triassic tetrapod and in a phytosaur.     

IL-1beta synthesis by chondrocyte analyzed by 3D microscopy and flow cytometry: effect of Rhein

Several factors are known to be involved in the destruction of the articular cartilage. Interleukin-1 (IL-1) plays an important role in the pathogenesis of osteoarthritis (OA) either directly or through the stimulation of catabolic factors. The action of IL-1 on articular cartilage is multifaceted and it most likely plays an important role in the mechanism of cartilage destruction. IL-1 suppresses the synthesis of the cartilage matrix components and promotes the degradation of cartilage matrix macromolecules. Diacerein is an anthraquinone molecule that has been shown to reduce the severity of OA, both in man and in animal models. The present study was designed to evaluate in vitro effects of diacerein on IL-1beta expression in LPS or IL-1alpha stimulated chondrocytes. Intracellular IL-1beta production was analysed in articular chondrocytes cultured in monolayer or in alginate 3D-biosystems in the presence of lipopolysaccharide (LPS) or IL-1alpha, with or without diacerein. The results show that LPS and IL-1alpha increase intracellular IL-1beta and Diacerein inhibited LPS-induced and IL-1alpha induced IL-1beta production by articular chondrocytes. Moreover, the effect of mechanical stimulation was analysed. An inhibitory effect of DAR at therapeutic concentrations on IL-1beta production in articular chondrocytes is suggested.     

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.