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OBJECTIVE

): Articular cartilage is roughly separated into 3 areas: the tangential, middle, and deep zones. The structure and molecular components of an additional important zone, the most superficial zone (MSZ), which directly faces the joint cavity, have yet to be conclusively elucidated. The purpose of the present study was to use multiple methods to study the MSZ in order to determine its structure. (MATERIALS AND

METHODS

): Knees from 16 pigs (age, 6 months) were used. Full-thickness cartilage specimens were harvested from the femoral groove. The MSZ was observed using light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) in combination with histochemical and immunohistochemical methods. (

RESULTS

): The combined findings from the 3 different observational methods indicate that the MSZ is subdivided into 3 layers. Among these 3 layers, collagen subtypes I, II, and III are present in the innermost (3rd) layer of the MSZ. Beneath the 3rd layer, type II collagen is the predominant type, with small amounts of type III collagen. This layer beneath the 3rd layer is considered to be the tangential layer. (

CONCLUSIONS

): Our observations indicate that the MSZ is subdivided into 3 layers. Further analysis of the molecular components in each layer may improve our understanding of the structure of the articular surface.

OBJECTIVE:

To correlate meniscal T2* relaxation times using ultra-short echo time (UTE) magnetic resonance imaging (MRI) with quantitative microscopic methods, and to determine the effect of meniscal repair on post-operative cartilage T2 values.

DESIGN:

A medial meniscal tear was created and repaired in the anterior horn of one limb of 28 crossbred mature ewes. MR scans for morphological evaluation, meniscal T2* values, and cartilage T2 values were acquired at 0, 4 and 8 months post-operatively for the Tear and Non-Op limb. Samples of menisci from both limbs were analyzed using multiphoton microscopy (MPM) analysis and biomechanical testing.

RESULTS:

Significantly prolonged meniscal T2* values were found in repaired limbs than in control limbs, p<0.0001. No regional differences of T2* were detected for either the repaired or control limbs in the anterior horn. Repaired limbs had prolonged cartilage T2 values, primarily anteriorly, and tended to have lower biomechanical force to failure at 8 months than Non-Op limbs. MPM autofluorescence and second harmonic generation data correlated with T2* values at 8 months (ρ=-0.48, p=0.06).

CONCLUSIONS:

T2* mapping is sensitive to detecting temporal and zonal differences of meniscal structure and composition. Meniscal MPM and cartilage T2 values indicate changes in tissue integrity in the presence of meniscal repair.

OBJECTIVES:

To recommend a consensus-derived set of performance-based tests of physical function for use in people diagnosed with hip or knee osteoarthritis (OA) or following joint replacement.

METHODS:

An international, multidisciplinary expert advisory group was established to guide the study. Potential tests for consideration in the recommended set were identified via a survey of selected experts and through a systematic review of the measurement properties for performance-based tests. A multi-phase, consensus-based approach was used to prioritize and select performance-based tests by applying decision analysis methodology (1000Minds software) via online decision surveys. The recommended tests were chosen based on available measurement-property evidence, feasibility of the tests, scoring methods and expert consensus.

RESULTS:

Consensus incorporated the opinions of 138 experienced clinicians and researchers from 16 countries. The five tests recommended by the advisory group and endorsed by OARSI were the 30-second chair stand test, 40m fast-paced walk test, a stair climb test, timed up and go test and six-minute walk test. The first three were recommended as the minimal core set of performance-based tests for hip or knee OA.

CONCLUSION:

The OARSI recommended set of performance-based tests of physical function represents the tests of typical activities relevant to individuals diagnosed with hip or knee OA and following joint replacements. These tests are complementary to patient-reported measures and are recommended as prospective outcome measures in future OA research and to assist decision making in clinical practice. Further research should be directed to expanding the measurement-property evidence of the recommended tests.

OBJECTIVE:

The degeneration of articular cartilage is part of the clinical syndrome of osteoarthritis (OA) and one of the most common causes of pain and disability in middle-aged and older people [1]. However, the objective detection of an initial state of OA is still challenging. In order to categorize cartilage into states of OA, an algorithm is presented which offers objective categorization on the basis of 2-photon laser-scanning microscopy (TPLSM) images.

METHODS:

The algorithm is based on morphological characteristics of the images and results in a topographical visualization. This paper describes the algorithm and shows the result of a categorization of human cartilage samples.

RESULTS:

The resulting map of the analysis of TPLSM images can be divided into areas which correspond to the grades of the Outerbridge categorization. The algorithm is able to differentiate the samples in coincidence with the macroscopic impression.

CONCLUSION:

The method is promising for early OA detection and categorization. In order to achieve a higher benefit for the physician the method must be transferred to an endoscopic setup for an application in surgery.

OBJECTIVE:

This study aimed to evaluate the structural benefit of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in an hydrogel (H) derived from chitosan on the development of osteoarthritis (OA) in rabbit.

DESIGN:

OA was induced by the surgical transection of the anterior cruciate ligament in rabbits. Animals received a single intra-articular injection (900 μl) of AC beads in H hydrogel, H hydrogel alone or saline one week after surgery. OA development was followed by X-rays. Blood samples were collected throughout the study to measure biological markers (PGE2 and CRP). Macroscopic observation and histological evaluation of articular cartilage and synovial membrane were performed 6 weeks after surgery.

RESULTS:

AC beads in H hydrogel prevented from the development of OA based on the reduction of the Kellgren & Lawrence (K&L) score. It also significantly reduced the histological score of cartilage lesion severity. This effect was homogenous on every joint compartment. It was due to a significant effect on cartilage structure and cellularity scores. The injection of AC beads in H hydrogel also tended to reduce the synovial membrane inflammation. No significant variation of biological markers was noted.

CONCLUSIONS:

The present pilot study provides interesting and promising results for the use of AC beads in H hydrogel in animal. It indeed prevented the development of OA cartilage lesions without inflammatory signs. The potencies of this biomaterial to protect OA joint should be further documented. It could then represent a new alternative for viscosupplementation in human OA management.

OBJECTIVE:

Cam-type femoroacetabular impingement (FAI) deformities have been associated with early osteoarthritic degeneration of the hip. Degeneration depends on many factors such as joint morphology and dynamics of motion. Bone mineral density (BMD) appears to be a manifestation of the above, and may be a potentiater. Thus the goal of this study was to assess subchondral BMD of cam deformities in symptomatic and asymptomatic FAI subjects, and to compare to normal controls.

METHODS:

Subjects undergoing surgical correction of a symptomatic cam-type deformity were recruited ("Surgical"). Asymptomatic volunteers were also recruited and classified as normal ("Control") or having a deformity ("Bump") based on their alpha angle measurement. All subjects (n=12 per group) underwent CT with a calibration phantom. BMD was determined in volumes of interest around the femoral head and neck to a depth of 5 mm. BMD was compared between groups in each section using spine BMD as a covariate.

RESULTS:

No differences were seen between groups in the peripheral bearing surface. The Bump group exhibited higher BMD than Controls within the head/neck junction (p<0.05). When compared to normal subchondral bone in the peripheral level of Controls, BMD in the deformity was up to 78% higher in Bump subjects and up to 47% higher Surgical subjects (p<0.05).

CONCLUSION:

Subchondral BMD of cam deformities is higher than that of normal subchondral bone in the peripheral region of the femoral head, regardless of symptom status. The expected increased subchondral stiffness may increase contact stresses in the joint tissues leading to accelerated degeneration.

OBJECTIVE:

To examine whether the ratio of the 2(nd) and 4(th) metacarpal bone length (MC2:MC4) in subjects with prior meniscectomy of the knee is associated with radiographic hand and knee osteoarthritis (OA) and its progression.

DESIGN:

We assessed 219 subjects (175 men and 44 women) twice with a follow-up time ranging from 4 to 10 years. Participants had all undergone prior meniscectomy. The subjects were of mean (SD) 53 (11) years of age at the first radiographic examination. One observer measured the metacarpal lengths of both hands. We used the average MC2:MC4 from left and right hand divided into tertiles as the exposure variable, using the highest tertile, i.e., "female" pattern as reference category. Radiographic OA of both hands and knees and its progression were evaluated on subject level as our outcomes. We used logistic regression to evaluate the possible association of MC2:MC4 with hand and knee OA and its progression with adjustment for age, sex, body mass index, and follow-up time.

RESULTS:

We found no statistically significant association between the lower MC2:MC4 tertile "male" pattern and prevalent hand OA (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.24-1.99) and prevalent knee OA (OR 1.08; 95% CI 0.56-2.07). Neither did we find any corresponding significant association for the progression of hand OA (OR 0.89; 95% CI 0.34-2.32), nor knee OA (OR 0.69; 95% CI 0.33-1.46).

CONCLUSIONS:

We did not detect any association between MC2:MC4 and radiographic hand and knee OA and its progression in subjects with prior meniscectomy.

The 6th OARSI Workshop on Imaging in Osteoarthritis combined with the 3rd osteoarthritis (OA) Biomarkers Workshop is the first to bring together the imaging and molecular biomarker communities to focus on clinical validation and qualification of OA biomarkers. The workshop was held in Hilton Head, SC, USA, from June 12-14, 2012; 138 attendees participated, including representatives from academia, pharmaceutical and magnetic resonance imaging (MRI) industries, Food and Drug Administration (FDA), and NIH. Presentations and discussions raised awareness, consolidated knowledge, and identified strategies to overcome challenges for the development and application of imaging and biochemical biomarkers in OA research studies and clinical trials.

CONCLUSION:

The OA research communities need to work alongside regulatory agencies across the world, to qualify and validate new chemical and imaging biomarkers for future research and clinical trials.

OBJECTIVE:

The aim of this study was to compare the early repair response of cartilage defects in trochlea (TR) and medial femoral condyle (MFC) at 2-3 weeks after bone marrow stimulation.

DESIGN:

Bilateral full-thickness cartilage defects were generated in central trochlear groove and MFC of skeletally mature rabbits. Four subchondral perforations were made on each defect, either by microfracture to 2 mm deep, or by drilling to 2 mm or 6 mm deep. Rabbits were sacrificed either on Day 14 post-operatively or on Day 21. Defects were analyzed by histology, stereology, histomorphometry and micro-computed tomography (CT). Intact femurs (N = 4) served as controls.

RESULTS:

Stromal cell density recruitment was similar in all defects, irrespective of defect location and surgical techniques used. There was a robust appearance of chondrocytes at Day 21 in TR defects with significantly higher volume fraction of chondrocytes in TR compared to MFC (P = 0.013). Chondrogenic foci were observed in marrow penetrating holes, with a significantly higher frequency and larger foci in TR vs MFC defects at Day 21 (P = 0.043 and P = 0.0014, respectively). Micro-CT analysis showed that deep drilling elicited significantly more mineralized bone fill compared to shallower perforations at 2 and 3 weeks repair (all at P ≤ 0.0008).

CONCLUSIONS:

Bone marrow stimulation induced greater chondrogenesis in TR vs MFC defects in adult rabbits, with more chondrocytes and larger chondrogenic foci appearing in TR vs MFC on Day 21 post-operation.

OBJECTIVE:

Pro-inflammatory cytokines play an important role in inducing cartilage degradation during osteoarthritis pathogenesis. Muscle is a tissue that lies near cartilage in situ. However, muscle's non-loading biochemical effect on cartilage has been largely unexplored. Here, we tested the hypothesis that muscle cells can regulate the response to pro-inflammatory cytokine-mediated damage in chondrocytes derived from human mesenchymal stem cells (hMSCs).

METHOD:

hMSCs were allowed to undergo chondrogenic differentiation in porous silk scaffolds in the typical chondrogenic medium for 12 days. For the next 9 days, the cells were cultured in chondrogenic medium containing 50% conditioned medium derived from C2C12 muscle cells or fibroblast control cells, and were subject to treatments of pro-inflammatory cytokines IL-1β or TNFα.

RESULTS:

Both IL-1β and TNFα-induced strong expression of multiple MMPs and hypertrophic markers Runx2 and type X collagen. Strikingly, culturing hMSC-derived chondrocytes in C2C12 muscle cell-conditioned medium strongly inhibited the expression of all these genes, a result further confirmed by GAG content and histological evaluation of matrix protein. To determine whether these effects were due to altered chondrocyte growth and survival, we assayed the expression of cell proliferation marker Ki67, cell cycle arrest markers p21 and p53, and apoptosis marker caspase 3. Muscle cell-conditioned medium promoted proliferation and inhibited apoptosis, thereby suggesting a possible decrease in the cellular aging and death that typically accompanies cartilage inflammation.

CONCLUSION:

Our findings suggest the role of muscle in cartilage homeostasis and provide insight into designing strategies for promoting resistance to pro-inflammatory cytokines in hMSC-derived chondrocytes.