Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics

SummaryObjectiveOsteoarthritis (OA) is characterized by the changes in structure and composition of articular cartilage. However, it is not fully known, what is the depth-wise change in two major components of the cartilage solid matrix, i.e., collagen and proteoglycans (PGs), during OA progression. Further, it is unknown how the depth-wise changes affect local tissue strains during compression. Our aim was to address these issues.MethodsData from the previous microscopic and biochemical measurements of the collagen content, distribution and orientation, PG content and distribution, water content and histological grade of normal and degenerated human patellar articular cartilage (n=73) were reanalyzed in a depth-wise manner. Using this information, a composition-based finite element (FE) model was used to estimate tissue function solely based on its composition and structure.ResultsThe orientation angle of collagen fibrils in the superficial zone of cartilage was significantly less parallel to the surface (P<0.05) in samples with early degeneration than in healthy samples. Similarly, PG content was reduced in the superficial zone in early OA (P<0.05). However, collagen content decreased significantly only at the advanced stage of OA (P<0.05). The composition-based FE model showed that under a constant stress, local tissue strains increased as OA progressed.ConclusionFor the first time, depth-wise point-by-point statistical comparisons of structure and composition of human articular cartilage were conducted. The present results indicated that early OA is primarily characterized by the changes in collagen orientation and PG content in the superficial zone, while collagen content does not change until OA has progressed to its late stage. Our simulation results suggest that impact loads in OA joint could create a risk for tissue failure and cell death

Development of frequency domain multiplexing for the X-ray Integral Field Unit (X-IFU) on the Athena

We are developing the frequency domain multiplexing (FDM) read-out of transition-edge sensor (TES) microcalorimeters for the X-ray Integral Field Unit (X-IFU) instrument on board of the future European X-Ray observatory Athena. The X-IFU instrument consists of an array of $\sim$3840 TESs with a high quantum efficiency ($>$90 \%) and spectral resolution $\Delta E$=2.5 eV $@$ 7 keV ($E/\Delta E\sim$2800). FDM is currently the baseline readout system for the X-IFU instrument. Using high quality factor LC filters and room temperature electronics developed at SRON and low-noise two stage SQUID amplifiers provided by VTT, we have recently demonstrated good performance with the FDM readout of Mo/Au TES calorimeters with Au/Bi absorbers. An integrated noise equivalent power resolution of about 2.0 eV at 1.7 MHz has been demonstrated with a pixel from a new TES array from NASA/Goddard (GSFC-A2). We have achieved X-ray energy resolutions $\sim$2.5 eV at AC bias frequency at 1.7 MHz in the single pixel read-out. We have also demonstrated for the first time an X-ray energy resolution around 3.0 eV in a 6 pixel FDM read-out with TES array (GSFC-A1). In this paper we report on the single pixel performance of these microcalorimeters under MHz AC bias, and further results of the performance of these pixels under FDM.Comment: 8 pages, 4 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2014: Ultraviolet to Gamma Ray

Repair of osteochondral defects with recombinant human type II collagen gel and autologous chondrocytes in rabbit

SummaryObjectiveRecombinant human type II collagen (rhCII) gels combined with autologous chondrocytes were tested as a scaffold for cartilage repair in rabbits in vivo.MethodAutologous chondrocytes were harvested, expanded and combined with rhCII-gel and further pre-cultivated for 2 weeks prior to transplantation into a 4 mm diameter lesion created into the rabbit's femoral trochlea (n = 8). Rabbits with similar untreated lesions (n = 7) served as a control group.ResultsSix months after the transplantation the repair tissue in both groups filled the lesion site, but in the rhCII-repair the filling was more complete. Both repair groups also had high proteoglycan and type II collagen contents, except in the fibrous superficial layer. However, the integration to the adjacent cartilage was incomplete. The O'Driscoll grading showed no significant differences between the rhCII-repair and spontaneous repair, both representing lower quality than intact cartilage. In the repair tissues the collagen fibers were abnormally organized and oriented. No dramatic changes were detected in the subchondral bone structure. The repair cartilage was mechanically softer than the intact tissue. Spontaneously repaired tissue showed lower values of equilibrium and dynamic modulus than the rhCII-repair. However, the differences in the mechanical properties between all three groups were insignificant.ConclusionWhen rhCII was used to repair cartilage defects, the repair quality was histologically incomplete, but still the rhCII-repairs showed moderate mechanical characteristics and a slight improvement over those in spontaneous repair. Therefore, further studies using rhCII for cartilage repair with emphasis on improving integration and surface protection are required

Craniometric Analysis of the Hindbrain and Craniocervical Junction of Chihuahua, Affenpinscher and Cavalier King Charles Spaniel Dogs With and Without Syringomyelia Secondary to Chiari-Like Malformation

Objectives To characterize and compare the phenotypic variables of the hindbrain and craniocervical junction associated with syringomyelia (SM) in the Chihuahua, Affenpinscher and Cavalier King Charles Spaniel (CKCS). Method Analysis of 273 T1-weighted mid-sagittal DICOM sequences of the hindbrain and craniocer-vical junction from 99 Chihuahuas, 42 Affenpinschers and 132 CKCSs. The study compared 22 morphometric features (11 lines, eight angles and three ratios) of dogs with and without SM using refined techniques based on previous studies of the Griffon Bruxellois (GB) using Discriminant Function Analysis and ANOVA with post-hoc corrections. Results The analysis identified 14/22 significant traits for SM in the three dog breeds, five of which were identical to those reported for the GB and suggest inclusion of a common aetiology. One ratio, caudal fossa height to the length of the skull base extended to an imaginary point of alignment between the atlas and supraoccipital bones, was common to all three breeds (p values 0.029 to <0.001). Associated with SM were a reduced occipital crest and two acute changes in angulation i) 'sphenoid flexure' at the spheno-occipital synchondrosis ii) 'cervical flexure' at the foramen magnum allied with medulla oblongata elevation. Comparing dogs with and without SM, each breed had a unique trait: Chihuahua had a smaller angle between the dens, atlas and basioccipital bone (p value <0.001); Affenpinschers had a smaller dis-tance from atlas to dens (p value 0.009); CKCS had a shorter distance between the spheno-occipital synchondrosis and atlas (p value 0.007). Conclusion The selected morphometries successfully characterised conformational changes in the brain and craniocervical junction that might form the basis of a diagnostic tool for all breeds. The severity of SM involved a spectrum of abnormalities, incurred by changes in both angulation and size that could alter neural parenchyma compliance and/or impede cerebrospinal fluid channels.Peer reviewe

Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs

OBJECTIVE: To monitor the concentration of markers of cartilage and synovium metabolism in the knee (stifle) joint synovial fluid of young beagles subjected to immobilisation and subsequent remobilisation.METHODS: The right hind limb of 17 dogs was immobilised in flexion for 11 weeks. Simultaneously, the contralateral left knee was exposed to increased weight bearing. The remobilisation period lasted 50 weeks. Litter mates served as controls. The concentration in joint lavage fluid of interleukin 1 (IL1) was measured by immunoassay, the activity of phospholipase A2 (PLA2) was determined by an extraction method, chondroitin sulphate (CS) concentration by precipitation with Alcian blue, hyaluronan (HA) by an ELISA-like assay using biotinylated HA-binding complexes, matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinases 1 (TIMP-1) by sandwich ELISA, and synovitis was scored by light microscopy.RESULTS: Synovitis or effusion was absent in all experimental and control groups. Immobilisation decreased the joint lavage fluid levels of IL1 (p<0.05), TIMP (p< 0.05), and the concentration of CS down to 38 (p<0.05) in comparison with untreated litter mates with normal weight bearing. Immobilisation did not affect the activity of PLA2, or the concentration of MMP-3 or HA in synovial fluid. Joint remobilisation restored the decreased concentrations of markers to control levels. Increased weight bearing did not change the concentrations of markers in comparison with the control joints with normal weight bearing.CONCLUSIONS: 11 weeks joint immobilisation decreased the concentration of markers of cartilage and synovium metabolism in the synovial fluid, and remobilisation restored the concentrations to control levels. The changes in joint metabolism induced by immobilisation, as reflected by the markers, are thus different from those found in osteoarthritis, where increased levels of these markers are associated with enhanced degradation and synthesis. These findings suggest that the change induced in joint metabolism by immobilisation is reversible in its early stages

Targeted re-sequencing of linkage region on 2q21 identifies a novel functional variant for hip and knee osteoarthritis

Objective: The aim of the study was to identify genetic variants predisposing to primary hip and knee osteoarthritis (OA) in a sample of Finnish families. Methods: Genome wide analysis was performed using 15 independent families (279 individuals) originating from Central Finland identified as having multiple individuals with primary hip and/or knee OA. Targeted re-sequencing was performed for three samples from one 33-member, four-generation family contributing most significantly to the LOD score. In addition, exome sequencing was performed in three family members from the same family. Results: Genome wide linkage analysis identified a susceptibility locus on chromosome 2q21 with a multipoint LOD score of 3.91. Targeted re-sequencing and subsequent linkage analysis revealed a susceptibility insertion variant rs11446594. It locates in a predicted strong enhancer element region with maximum LOD score 3.42 under dominant model of inheritance. Insertion creates a recognition sequence for ELF3 and HMGA1 transcription factors. Their DNA-binding affinity is highly increased in the presence of A-allele compared to wild type null allele. Conclusion: A potentially novel functional OA susceptibility variant was identified by targeted resequencing. This variant locates in a predicted regulatory site and creates a recognition sequence for ELF3 and HMGA1 transcription factors that are predicted to play a significant role in articular cartilage homeostasis. (C) 2015 The Authors. Published by Elsevier Ltd and Osteoarthritis Research Society International.Peer reviewe

Kotimaisen järvi- ja merikalan dioksiinien, furaanien, dioksiinien kaltaisten PCB-yhdisteiden ja polybromattujen difenyylieettereiden pitoisuudet

EU-kalat -projekti toteutettiin, koska haluttiin saada tietoa kotimaisen kalan sisältämistä ympäristömyrkkypitoisuuksista. Tietoa päätettiin hankkia sekä Itämeren kalan että sisävesikalojen tärkeimmistä ympäristömyrkyistä: dioksiineista, joille oli asetettu EU:ssa enimmäispitoisuusraja, PCB-yhdisteistä, joiden sääntelyä EU:ssa osattiin odottaa, bromatuista difenyylieettereistä, joiden tiedettiin kertyvän kalaan sekä myös raskasmetalleista (julkaistaan erillisenä julkaisuna), joiden sääntelyä EU:ssa oli tarve tarkistaa. Suomen oli täytettävä myös ne edellytykset, jotka EU oli asettanut antaessaan Suomelle ja Ruotsille erityiskohtelun dioksiineja koskevassa lainsäädännössä. Lisäksi oli kiinnitettävä huomiota myös kotimaisen kalan sisältämien epäpuhtauksien aiheuttamiin seurauksiin kalastajille ja kalanjalostusteollisuudelle. Tutkimuksesta ilmeni, että dioksiinien ja PCB-yhdisteiden kertyminen kalaan on ennen kaikkea kalalajin ominaisuus. Ongelmakaloiksi jäivät lohi ja suurikokoinen silakka tässä järjestyksessä. Molemmista analysoitiin moninkertaisia pitoisuuksia dioksiineja enimmäispitoisuuteen (4 pg TEQ/g tuorepainoa) verrattuna. Sekä silakalla että lohella dioksiinipitoisuudet korreloivat iän mukana; mitä vanhempi kala sitä enemmän dioksiineja. Kaikki muut kotimaiset kalat paria poikkeuksellista tutkimustulosta lukuun ottamatta alittavat dioksiinille asetetun enimmäispitoisuusrajan. Myös kasvatetun kalan dioksiinipitoisuudet jäävät selvästi alle enimmäispitoisuusrajan

Long-term clinical and radiographic outcomes and patient satisfaction after adult spinal deformity correction

Background and Aims: Adult spinal deformity surgery has increased with the aging population and modern surgical approaches, although it has high complication and reoperation rates. The permanence of radiographic correction, mechanical complications, predictive factors for poor patient-reported outcomes, and patient satisfaction were analyzed. Material and Methods: A total of 79 adult patients were retrospectively analyzed at baseline and 1-9 years after adult spinal deformity correction between 2007 and 2016. Patient-reported outcomes (Oswestry Disability Index, visual analog scale, and Scoliosis Research Society-30 scores), changes in radiographic alignment, indications for reoperation, predictors of poor outcomes according to the Oswestry Disability Index and Scoliosis Research Society-30 scores, and patient satisfaction with management were studied. Results: Oswestry Disability Index and visual analog scale scores (p = 0.001), radiographic correction of thoracic kyphosis, lumbar lordosis, and pelvic retroversion (pPeer reviewe