OBJECTIVE: To investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls.
METHODS: Quantitative double-echo steady-state (qDESS) 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20-30 years: healthy, HEA20-30, n=24; ACL-injured, ACL20-30, n=23; 40-60 years: healthy, HEA40-60, n=24; ACL-injured, ACL40-60, n=14 (ACL injury 2-10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side difference in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics.
RESULTS: Cartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL20-30 than in HEA20-30. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls.
CONCLUSIONS: In the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in the diagnosing and monitoring early articular cartilage changes.

OBJECTIVE: Chondrocyte-based cell therapies are effective for the treatment of chondral lesions, but remain poorly indicated for diffuse lesions in the context of early osteoarthritis (OA). The aim of this study was to develop a protocol to obtain chondroprogenitor cells suitable for the treatment of diffuse chondral lesions within early OA.
METHODS: Cartilage cells were expanded at low density in human platelet lysate (hPL). A test was performed to exclude senescence. The expression of surface cluster of differentiation 146, cluster of differentiation 166, major histocompatibility complex (MHC)-I and MHC-II and of genes of interest were evaluated, as well as the trophic potential of these cells, by the assessment of lubricin and matrix production. The immunomodulatory potential was assessed through their co-culture with macrophages.
RESULTS: Cartilage cells expanded at low density in hPL showed higher proliferation rate than standard-density cells, no replicative senescence, low immunogenicity and expression of lubricin. Moreover, they presented an increased expression of chondrogenic and antihypertrophic markers, as well as a superior matrix deposition if compared to cells cultured at standard density. Cartilage cells induced on macrophages an upregulation of CD206, although a higher increase of CD163 expression was observed in the presence of low-density cells.
CONCLUSIONS: These findings lay the grounds to explore the clinical usefulness of low-density cultured cartilage cells to treat diffuse lesions in early OA joints for both autologous and allogenic use.
METHODS: Not applicable.

UNASSIGNED: Chronic inflammation and altered walking biomechanics are common after ACL reconstruction (ACLR) and contribute to the development of osteoarthritis. Clinically accessible techniques are needed to monitor inflammation (ultrasound-assessed effusion-synovitis) and walking biomechanics (force-measuring insoles), and they must improve the translation of these assessments and determine whether inflammation and walking biomechanics are related in patients after ACLR. This study aimed to determine the association between ultrasound-detected knee effusion-synovitis and limb loading asymmetries during walking in patients 1-5 years post-ACLR.
UNASSIGNED: 15 participants (9 women; age: 26 ± 6yrs; mass: 71 ± 15 kg; height: 173 ± 9 cm; months post-ACLR: 29 ± 13) were included in this cross-sectional study. Knee effusion-synovitis was assessed using a standardized protocol and graded using a validated scoring atlas (0 = absent, 1 = mild, 2 = moderate, 3 = severe) in the ACLR limb. Force-measuring insoles were used to capture the vertical ground reaction force (vGRF) during a one-minute treadmill walking trial. Limb symmetry indices (LSIs) were used to quantify limb loading asymmetry for the peak vGRF and the instantaneous loading rate (vGRF-LR). Spearman correlations determined whether effusion-synovitis grade was associated with peak vGRF and vGRF-LR LSI.
UNASSIGNED: Effusion-synovitis was present in the ACLR limb of 13/15 (87 %) participants (Grade 0: n = 2; Grade 1: n = 8; Grade 2: n = 4, Grade 3: n = 1). Effusion-synovitis grade was not significantly associated with peak vGRF LSI (mean±sd: 98.0 ± 5.6; ρ = 0.38, p = 0.162), but was significantly associated with vGRF-LR LSI (98.2 ± 11.4; ρ = 0.55, p = 0.035).
UNASSIGNED: Most participants 1-5 years post-ACLR have ultrasound-detected effusion-synovitis. Participants with more severe effusion-synovitis load their ACLR limb more rapidly. This study highlights the utility of clinically accessible techniques in assessing inflammation and walking biomechanics in ACLR patients.

This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.

UNASSIGNED: It is unclear which factors are associated with a successful total hip arthroplasty (THA) in patients with early radiographic osteoarthritis (OA).
UNASSIGNED: 70 patients with early OA (Kellgren and Lawrence [KL] grades 0-2) who underwent THA were compared with 200 patients with advanced OA (KL grades 3-4). Outcomes were Oxford Hip Scores (OHS), EQ-5D and EQ-VAS scores; compared preoperatively with 1 year postoperatively. We investigated which clinical and radiographic (plain x-ray, CT, MRI) features predicted successful THA (postoperative OHS ⩾42).
UNASSIGNED: The early OA group were significantly younger (61 vs. 66 years; [p = 0.0035). There were no significant differences in BMI, ASA grade or gender. After adjusting for confounders, the advanced OA group had a significantly greater percentage of possible change (PoPC) in OHS (75.8% vs. 50.4%; p < 0.0001) and improvement in EQ-5D (0.151 vs. 0.002; p < 0.0001). There were no significant differences in complication, revision or readmission rates. In the early OA group, 16/70 (22.9%) patients had a \'successful\' THA. Patients who had a \'successful\' THA were significantly more likely to have subchondral cysts on CT/MRI (91.7% vs. 57.7%; p = 0.0362). The presence of cysts on CT/MRI was associated with a significantly greater PoPC in OHS (61.6% vs. 38.2%; p = 0.0353). The combination of cysts and joint space width <1 mm was associated with a PoPC of 68%.
UNASSIGNED: THA in patients with early OA (KL grades 0-2) on plain radiographs should be indicated with caution. We advocate preoperative cross-sectional imaging in these patients. In the absence of cysts on CT/MRI, a THA seems unlikely to provide a satisfactory outcome.

OBJECTIVE: Osteoarthritis (OA) is a combination of degeneration and destruction of articular cartilage due to mechanical stress, secondary synovitis, and bone remodelling. In recent years, early knee OA, a preliminary stage of structural failure in OA, has attracted attention as a potential target for therapy to prevent the onset of OA. Intra-articular administration of monoiodoacetic acid (MIA) induces OA-like symptoms, and low doses of MIA induce early OA like symptoms. In this experiment, a low-dose of MIA was induced to early OA model mice, which were then irradiated with low-intensity pulsed ultrasound (LIPUS) to examine whether LIPUS improves symptoms of early OA.
METHODS: After 4 weeks of LIPUS irradiation, articular cartilage was observed at 1 and 4 weeks. The Osteoarthritis Research Society International (OARSI) scores were calculated using Safranin-O staining results. Cartilage degeneration was detected using Denatured Collagen Detection Reagent (DCDR).
RESULTS: We observed a significant decrease in OARSI scores in the LIPUS irradiated group at week 4. The non-LIPUS group showed widespread areas of double positivity for Type II collagen and DCDR, whereas the LIPUS group showed only a small number of DCDR-positive areas. In addition, macrophage numbers counted in the articular capsule at week 1 showed a significant decrease in the LIPUS irradiated group. Lubricin detection showed that lubricin positive cell number was significantly increased by LIPUS irradiation at week 4.
CONCLUSIONS: These results suggest that LIPUS attenuates cartilage degeneration in early OA by relieving inflammation and enhancing the inhibitory effect of lubricin on cartilage degeneration.

OBJECTIVE: Ultra-short TE (UTE) sequences on MRI are a technique that improves the visualization of tissues with short T2 relaxation time, such as deep cartilage layers. In addition, T2* relaxation time calculated from the UTE has the potential to evaluate water molecules bound to the cartilage matrix. This study was performed to determine if there is an association between UTE-T2* relaxation time by cartilage layer and histological degeneration in knee osteoarthritis (OA).
METHODS: Seven knees that had undergone total knee arthroplasty (TKA) were included in the study, and the lateral tibial cartilage, which had the least degeneration of the resected bones, was used as the sample. The T2* relaxation time of 4 patients with no abnormal findings on MRI was the reference relaxation time. Histological degeneration of TKA samples was assessed by the Mankin score and graded as the early OA group (≤3 points) and the advanced OA group (≥4 points). The association between T2* relaxation time and Mankin grade in each cartilage layer was compared. The effect of angiogenesis to the tidemark on T2* relaxation time was also compared.
RESULTS: T2* relaxation time of the cartilage layer was significantly longer in early OA than that in the control group. In the deep cartilage layer, the mean T2* relaxation time for angiogenesis (-) was 15.7 ms, whereas it was significantly shorter for angiogenesis (+) at 8.2 ms.
CONCLUSIONS: The UTE-T2* relaxation time was associated with histological cartilage degeneration, suggesting a potential application in monitoring early cartilage degeneration.

The concept of early osteoarthritis (OA) is based on the expectation that if found and treated in the early stage, the progression of the disease might be arrested before affected joints are irreversibly destroyed. This notion of early OA detection can also bear meaning for regenerative medicine (RM) which is purposed to cure a disease by regenerating the damaged tissue. RM can be a category of disease-modifying osteoarthritis drugs (DMOADs) and provide an attractive treatment for OA, restoring structural damage incurred during the disease by repopulating cells and reconstituting. While cell therapy including the use of stem cells is conflated with RM, it may also comprise gene therapy, exosomes, and other cell or cell-free-derived products. Considering that not all early OA will become advanced OA and that RM has a characteristic of personalized medicine, it would be very important to foretell, even roughly, which patients will progress rapidly and who will favorably respond to regenerative treatment. Subclassification and comprehensive endotyping or phenotyping (E/P) can be very helpful in detecting the population who would benefit from RM as well as rapid progressors who need closer monitoring.

Early diagnosis of osteoarthritis (OA) is critical for effective cartilage repair. However, lack of blood vessels in articular cartilage poses a barrier to contrast agent delivery and subsequent diagnostic imaging. To address this challenge, we proposed to develop ultra-small superparamagnetic iron oxide nanoparticles (SPIONs, 4 nm) that can penetrate into the matrix of articular cartilage, and further modified with the peptide ligand WYRGRL (particle size, 5.9 nm), which allows SPIONs to bind to type II collagen in the cartilage matrix and increase the retention of probes. Type II collagen in the cartilage matrix is gradually lost with the progression of OA, consequently, the binding of peptide-modified ultra-small SPIONs to type II collagen in the OA cartilage matrix is less, thus presenting different magnetic resonance (MR) signals in OA group from the normal ones. By introducing the AND logical operation, damaged cartilage can be differentiated from the surrounding normal tissue on T1 and T2 AND logical map of MR images, and this was also verified in histology studies. Overall, this work provides an effective strategy for delivering nanosized imaging agents to articular cartilage, which could potentially be used to diagnosis joint-related diseases such as osteoarthritis.

Knee osteoarthritis (KOA) is one of the main problems of an aging society in terms of incidence, impairment to the quality of daily living (QOL), and economics. The main aim of this study was to verify the usefulness, in practical terms, of applying the existing diagnostic criteria of early knee osteoarthritis (EKOA). The secondary objective of this project was to evaluate the clinical progression of healthy subjects (HS) at risk of osteoarthritis and of patients with diagnosed EKOA. A cross-sectional longitudinal pilot study was carried out, in which 105 participants were classified as EKOA patients or HS according to the diagnostic criteria. Measures of disability, pain, and self-reported variables were assessed. Two follow-ups were performed in order to assess the diagnoses and radiological progression, and the clinical progression was evaluated using self-reported measures. Following the current diagnostic criteria, the participants were divided into EKOA and HS. Most of the participants did not present changes in their classification, although some subjects were reclassified as EKOA or HS in the follow-ups which were performed. The current classification criteria for EKOA based on self-reported measures, radiological findings, and clinical conditions such as pain could lead to a misdiagnosis of this process, as fluctuations in the classifications of patients according to their conditions were found during follow up.