Osteoarthritic Lesions Research Articles

Bone marrow lesions in knee osteoarthritis: regional differences in tibial subchondral bone microstructure and their association with cartilage degeneration

The aim of this study was to investigate how bone microstructure within bone marrow lesions (BMLs) relates to the bone and cartilage across the whole human tibial plateau. Thirty-two tibial plateaus from patients with osteoarthritis (OA) at total knee arthroplasty and eleven age-matched non-OA controls, were scanned exvivo by MRI to identify BMLs and by micro CT to quantitate the subchondral (plate and trabecular) bone microstructure. For cartilage evaluation, specimens were processed histologically. BMLs were detected in 75% of the OA samples (OA-BML), located predominantly in the anterior-medial (AM) region. In contrast to non-OA control and OA-no BML, in OA-BML differences in microstructure were significantly more evident between subregions. In OA-BML, the AM region contained the most prominent structural alterations. Between-group comparisons showed that the AM region of the OA-BML group had significantly higher histological degeneration (OARSI grade) (P<.0001, P<.05), thicker subchondral plate (P<.05, P<.05), trabeculae that are more anisotropic (P<.0001, P<.05), well connected (P<.05, P=n.s), and more plate-like (P<0.05, P<0.05), compared to controls and OA-no BML at this site. Compared to controls, OA-no BML had significantly higher OARSI grade (P<.0001), and lower trabecular number (P<.05). In established knee OA, both the extent of cartilage damage and microstructural degeneration of the subchondral bone were dependent on the presence of a BML. In OA-no BML, bone microstructural alterations are consistent with a bone attrition phase of the disease. Thus, the use of BMLs as MRI image-based biomarkers appear to inform on the degenerative state within the osteochondral unit.

Osteoarthritis patients with high haemoglobin A1c have increased Toll-like receptor 4 and matrix metalloprotease-13 expression in the synovium.

PurposeWhile research has identified diabetes mellitus (DM) as a risk factor for knee osteoarthritis (KOA), the underlying mechanisms are not fully understood. Studies suggest that Toll-like receptor 4 (TLR4) expression is elevated in osteoarthritic lesions of OA patients and in target tissues of insulin resistance such as adipose tissue and skeletal muscle in patients with DM. TLR4 is associated with inflammation and catabolic response via regulation of matrix metalloproteases (MMPs). We hypothesized that TLR4 and MMP expression may be increased in the synovial tissue (SYN) of KOA patients with diabetic pathology. We therefore investigated TLR and MMP expression in the SYN of KOA patients with and without high haemoglobin A1c concentrations.Patients and methodsA total of 171 patients radiographically diagnosed with KOA were grouped based on their HbA1c concentration (HbA1c ≥6.5 and HbA1c <6.5). We used real-time polymerase chain reaction to compare the expression of TLRs (TLR2, TLR4) and MMPs (MMP2, MMP3, MMP9 and MMP13) in patients’ SYN between the two groups. MMP13 regulation by the TLR4 ligand, lipopolysaccharide (LPS), in SYN cells was examined in culture by stimulating SYN cells with LPS or vehicle (culture medium) for 24 h.ResultsThe expression of TLR4 and MMP13 in the HbA1c ≥6.5 group was significantly elevated compared to that in the HbA1c <6.5 group. In contrast, TLR2, MMP2, MMP3 and MMP9 expression levels were similar between the groups. MMP13 mRNA and MMP13 protein levels in SYN cells were significantly higher following stimulation with LPS compared to vehicle.ConclusionsTLR4 and MMP13 expression were elevated in the synovium of osteoarthritis patients with high HbA1c concentrations. Our results may provide insight into the pathology of OA patients with DM.

The role of intra-articular administration of Fetuin-A in post-traumatic knee osteoarthritis: an experimental study in a rat model

BackgroundThe purpose of this study is to investigate the possible attenuating role of the intra-articular administration of Fetuin-A in post-traumatic secondary osteoarthritis in rats, and also its effect on the systematic levels of interleukins (ILs)-2,4,7, bone morphogenetic proteins (BMPs) 2, 4, 7, C-Reactive Protein (CRP) and Fetuin-A.MethodsThirty male Sprague Dawley rats were separated in two groups where post-traumatic osteoarthritis was induced surgically by Anterior Cruciate Ligament Transection and the transection of the Medial Collateral Ligament of the right knee. In the Control Group, only the surgical intervention took place. In Fetuin Group, along with the induction of osteoarthritis, a single dose of bovine fetuin was administrated intra-articularly, intra-operatively. Both groups were examined for 8 weeks. The levels of interleukins, bone morphogenetic proteins, Fetuin-A and C-Reactive Protein were evaluated by ELISA of peripheral blood in three time periods: preoperatively, 5 and 8 weeks post-operatively. Osteoarthritic lesions of the knee were classified according to the Osteoarthritis Research Society International Grading System and the Modified Mankin Score, by histologic examination.ResultsIL-2 levels were significantly decreased in the Fetuin Group. No statistical difference was signed on the levels of IL-7, BMP-2,4,7 and Fetuin-A between the two groups. CRP levels were significantly increased in the Fetuin Group in 5 weeks of the experiment. Fetuin Group signed better scores according to the OARSI classification system and Modified Mankin Score, without any statistical significance.ConclusionsIntra-articular administration of Fetuin-A restrictively affected the progression of post-traumatic arthritis in rats, as only the levels of IL-2 were decreased as well as limited osteoarthritic lesions were observed on the Fetuin Group.

Biplanar ultrasonografik incelemenin femoral artiküler kıkırdaktaki dejeneratif değişiklikleri saptamadaki tanı değeri

Aim: The aim of our study was to assess the diagnostic value of biplanar ultrasonography in detecting degenerative changes of femoral articular cartilage using magnetic resonance imaging as the reference method.Material and Methods: Femoral articular cartilage examination was performed with ultrasonography and magnetic resonance imaging in 40 patients with knee pain. Magnetic resonance imaging of the knees were carried out on a 1.5 T scanner with proton density weighted, fat suppressed sequence in three orthogonal planes. Ultrasonographic evaluations of the knees were performed in both longitudinal and transverse planes. Taking the findings of magnetic resonance imaging as a reference, the diagnostic effectiveness of biplanar US in detecting medial condylar, lateral condylar and intercondylar notch cartilage lesions were calculated.Results: The sensitivity of biplanar ultrasonography in detecting medial condylar, lateral condylar, and intercondylar notch cartilage lesions were 93.55%, 61.11%, and 53.85%, respectively. The specificity of the technique in detecting the lesions in these locations were 88.89%, 90.91%, and 100.00%, respectively. Conclusion: Ultrasonography is a relatively inexpensive, easily accessible and a non-invasive imaging tool. We found that biplanar ultrasonography is a reliable method in detecting medial condylar cartilage lesions in knee osteoarthritis, and we recommend using it for the purposes of screening and follow-up evaluation of medial type knee osteoarthritis where MRI is not accessible.

Noninvasive Mechanical Joint Loading as an Alternative Model for Osteoarthritic Pain.

ObjectiveMechanisms responsible for osteoarthritic (OA) pain remain poorly understood, and current analgesic therapies are often insufficient. This study was undertaken to characterize and pharmacologically test the pain phenotype of a noninvasive mechanical joint loading model of OA, thus providing an alternative murine model for OA pain.MethodsThe right knees of 12‐week‐old male C57BL/6 mice were loaded at 9N or 11N (40 cycles, 3 times per week for 2 weeks). Behavioral measurements of limb disuse and mechanical and thermal hypersensitivity were acquired before mechanical joint loading and monitored for 6 weeks postloading. The severity of articular cartilage lesions was determined postmortem with the Osteoarthritis Research Society International scoring system. To assess efficacy of various treatments for pain, 9N‐loaded mice were treated for 4 weeks with diclofenac (10 mg/kg), gabapentin (100 mg/kg), or anti–nerve growth factor (anti‐NGF) (3 mg/kg).ResultsMechanical hypersensitivity and weight bearing worsened significantly in 9N‐loaded mice (n = 8) and 11N‐loaded mice (n = 8) 2 weeks postloading, compared to baseline values and nonloaded controls. Maximum OA scores of ipsilateral knees confirmed increased cartilage lesions in 9N‐loaded mice (mean ± SEM 2.8 ± 0.2; P < 0.001) and 11N‐loaded mice (5.3 ± 0.3; P < 0.001), compared to nonloaded controls (1.0 ± 0.0). Gabapentin and diclofenac restored pain behaviors to baseline values after 2 weeks of daily treatment, and gabapentin was more effective than diclofenac. A single injection of anti‐NGF alleviated nociception 2 days after treatment and remained effective for 2 weeks, with a second dose inducing stronger and more prolonged analgesia.ConclusionOur findings show that mechanical joint loading induces OA lesions in mice and a robust pain phenotype that can be reversed using analgesics known to alleviate OA pain in patients. This establishes the use of mechanical joint loading as an alternative model for the study of OA pain.

Effects of cartilage progenitor cells and microRNA-140 on repair of osteoarthritic cartilage injury

To summarize the effect of cartilage progenitor cells (CPCs) and microRNA-140 (miR-140) on the repair of osteoarthritic cartilage injury, and analyze their clinical prospects. The recent researches regarding the CPCs, miR-140, and repair of cartilage in osteoarthritis (OA) disease were extensively reviewed and summarized. CPCs possess the characteristics of self-proliferation, expression of stem cell markers, and multi-lineage differentiation potential, and their chondrogenic ability is superior to other tissues-derived mesenchymal stem cells. CPCs are closely related to the development of OA, but the autonomic activation and chondrogenic ability of CPCs around the osteoarthritic cartilage lesion cannot meet the requirements of complete cartilage repair. miR-140 specifically express in cartilage, and has the potential to activate CPCs by inhibiting key molecules of Notch signaling pathway and enhance its chondrogenic ability, thus promoting the repair of osteoarthritic cartilage injury. Intra-articular delivery of drugs is one of the main methods of OA treatment, although intra-articular injection of miR-140 has a significant inhibitory effect on cartilage degeneration in rats, it also exhibit some limitations such as non-targeted aggregation, low bioavailability, and rapid clearance. So it is a good application prospect to construct a carrier with good safety, cartilage targeting, and high-efficiency for miR-140 based on articular cartilage characteristics. In addition, CPCs are mainly dispersed in the cartilage surface, while OA cartilage injury also begins from this layer, it is therefore essential to emphasize early intervention of OA. miR-140 has the potential to activate CPCs and promote the repair of cartilage injury in early OA, and it is of great clinical significance to further explore the role of miR-140 in OA etiology and to develop new OA treatment strategies based on miR-140.

Molecular changes in peripheral blood involving osteoarthritic joint remodelling.

Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty‐four six‐week‐old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene‐fold changes in PBLs were detected by a microarray analysis comparing rats that received 20‐week unilateral anterior crossbite (UAC) treatment with age‐matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA‐like lesions. The other twenty‐four rats were randomly placed in the UAC and control groups at 12‐ and 20‐week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real‐time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1‐positive, EXPH1‐positive and IL10‐positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation.

Meniscal Lesions in Geriatric Population: Prevalence and Association with Knee Osteoarthritis.

Objective: This study evaluated the prevalence of different types of meniscal lesions among elderly patients with knee pain. Moreover, this study assessed the relationship between meniscal lesions and the presence of radiographic knee osteoarthritis (OA) in the elderly population.Methods: The radiographs and magnetic resonance images of one knee out of 306 patients with knee pain aged 65-89 years were reviewed for knee OA and meniscal lesions. The prevalence of different types of meniscal lesions was calculated, and the relationship between the prevalence of meniscal lesion types and the presence of radiographic knee OA was analyzed.Results: Among 306 participants, 274 (89.5%) showed radiographic knee OA. We found one or more meniscal lesion(s) in 93% of the total subjects, in 94% of all patients with knee OA, and in 84% of all patients without knee OA. The prevalence of surgically target, possible-target, and non-target lesions were 24%, 72%, and 69%, respectively. The prevalence of surgically target lesions was significantly higher in patients with knee OA than in those without it. The most common lesion observed was meniscal extrusion, followed by the horizontal and complex meniscal tears.Conclusions: Our results demonstrated that meniscal damage is considerably prevalent among elderly individuals with knee pain, especially in those with knee OA. The fact that surgically target and possible-target lesions constitute a substantial proportion of these lesions should be considered in the clinical approach to these patients.

Influence of a posteromedial meniscocpsular injury on the tibiofemoral joint laxity: A cadaveric study

Objectives Up to 61% of meniscal tears can be associated with ACL ruptures. These lesions lead to anterior and rotary laxity increase. Posterior peripheral meniscocaspsular tear of medial meniscus is also called ramp lesion. Prevalence of this kind of lesion is 9% to 17% in adults and up to 23% in pediatric popultation. The aim of this study was to determined anterior laxity of cadaveric ACL deficient knees. Hypothesis was to find a correlation between size of ramp lesion and laxity in order to determine a threshold of size for which reparation is mandatory. Methods Twelve fresh cadaveric knees were explored for the study. Two knees was excluded because they presented major lesions of osteoarthritis and ACL and meniscal tears. 10 remaining knees were from 3 males and 2 females. Mean age at time of death was 86 years old. Dynamic laximetry with GNRB device was made in several conditions: Knee without any intervention, full of water knee, after ACL rupture and after ACL rupture and increasing sizes of ramp lesions up to 30 mm. Anteroposterior laxity was measured at each time with 3 kind of loading charge (134 N, 200 N and 250 N). Results After ACL section only, tibiofemoral joint anterior laxity was significatively increased. Mean increasing was 156% whatever is the loading force. No statistical laxity difference was find between knees with ACL tears only and knees with ACL and meniscal tears for each size of ramp lesions. Increasing size of ramp lesion was not correlated to increasing of laxity. We could not be able to determine a threshold for ramp lesion reparation. Conclusion: GNRB® is a valid device of knee laxity measure, escpecially for ACL deficient knee. Despite use of this performing tool, we can’t confirm our hypothesis. Stephen et al in 2015 have shown, with cadaveric study, significant increase of anterior tibial translation and rotary laxity in knees with extended ramp lesions. There is no data about a ramp lesion size threshold with clinical relevance. GNRB gives reliable measures of laxity in ACL deficient knees. We could not find a threshold size of ramp lesion which increase tibial anterior laxity. Cadaveric rotary laxity has to be also studied to find this threshold.

Populated collagen hydrogel and polyhydroxyalkanoate composites: novel matrices for cartilage repair and regeneration?

Purpose Articular cartilage is an avascular connective tissue present in joints which covers the ends of opposing bones providing a smooth, shock absorbing surface to promote normal joint function. Normal cartilage structure is maintained by chondrocytes, the only cell type present. Abnormal function/death of these cells, due to long- term “wear and tear” and other risk factors results in cartilage loss and osteoarthritis (OA). There is currently no cure for OA, the most common treatments simply involve the management of joint pain, or surgical treatments, which are not able to restore cartilage function. In recent years, cartilage repair has been approached with engineered scaffolds, able to support the growth of chondrocytes or progenitor cells to generate a neo-tissue, but the neo tissue generated is often fibrocartilage, mechanically inferior and less–durable than the hyaline cartilage normally found in healthy articular joints, indicating that further research is required to develop a more suitable scaffolds. The aim of this study has been to assess the properties of collagen I hydrogel 3D scaffolds, populated with the phenotypically stable chondrocytes cell line C20/A4, strengthened with solvent cast and 3D printed Polyhydroxyalkanoate (PHA) polymer. PHAs are a family of biopolyesters synthesized by bacteria with monomers of varying chain lengths (C4-C16) which can be blended to produce products with different mechanical properties. PHAs are biodegradable, non-toxic and biocompatible. It has been already established that PHA scaffolds are able to support chondrocyte growth and activity but despite that, they do not represent the natural environment for chondrocyte metabolism, collagen production and cartilage regeneration. A combination collagen hydrogel and PHA scaffold that addresses this issue would be highly desirable. Methods Polymer production and preparation PHAs were produced by Pseudomonas mendocina CH50 in batch fermentation conditions using a 15 L bioreactor with an operating fermenter volume of 10 L. with glucose as the sole carbon source under nitrogen limiting conditions. PHA film and scaffolds were either prepared using the solvent casting method incorporating large NaCl crystals (which were later dissolved out) to form a porous structure or with a 3D melt printing method. Collagen gel preparation and seeding: Type I collagen constructs were prepared with chondrocytes by mixing type I collagen polymer suspension with 10modified Eagle’s medium (MEM) and 1M NaOH solution was added dropwise, to neutralise the acidic gel mixture. This gel solution was then mixed with a cell suspension of C-20/A4 cells in Dulbecco’s MEM (DMEM)-based medium containing 1% foetal calf serum (FCS) . 1.2 ml constructs were cast in 24 well plates either on their own or with the addition of solvent cast PHA polymers or 3D printed PHA polymers. Gels were then allowed to solidify by incubation at 37 C for 5-10 minutes, overlaid with DMEM medium (1% FCS) and cultured for 1 or 7 days, at 37 C and 5% CO2. Compression Studies: Gels were subjected to compression, at 0,6KN/m2 for 5 minutes in a custom built apparatus. The displacement of gels was measured over time. Results The compression testing data demonstrates that type I collagen gels, seeded with C-20/A4 chondrocytes (control gels), exhibit changes in their mechanical properties over time, with an increased resistance and smaller displacement at Day 7 compare to Day 1. The addition of solvent cast and 3D printed scaffolds increase the mechanical resistance of the construct when compared to the populated control gels (collagen matix only) at DAY 1 and is even more evident at DAY 7. 3D printed scaffolds also show higher stiffness of the construct compared to the control and solvent cast polymer samples. Cytotoxicity testing performed with Alamar blue staining, on chondrocyte populations grown on PHA films, indicates that there are no cytotoxic effects of the polymer on cell viability at any of time points analysed over 7 days. Trypan Blue staining, after 5 minutes compression test, reveals no significant difference in viability in any of the samples containing PHA polymer (solvent cast or 3D printed) compare to control samples. Conclusions In conclusion, these studies suggest that a composite collagen gel-PHA construct provides a supportive environment for the maintenance of chondrocyte activity increasing the initial resistance of the structure to compression, whilst the embedded chondrocytes remodel the Type I collagen gel to form a more cartilage like structure. This may offer a potential application of collagen hydrogel-PHA scaffolds for clinical use in support of cartilage regeneration in small and contained osteoarthritic lesions.

Inhibition of sterol regulatory element-binding protein-2 alleviates high-fat diet-induced deterioration of knee cartilage: an osteoarthritis animal model study

Purpose: Previous studies demonstrate that modulated transcription factors of lipid metabolism, such as sterol regulatory element-binding protein-2 (SREBP-2), are involved in the pathogenesis processes of osteoarthritis (OA). However, the mechanism remains unclear. Here, we evaluated the expression of SREBP-2 and its target genes in cartilage from high-fat diet induced obese mice models. Methods: Baseline expression of SREBP-2 and its related genes was detected in the normal and DMM (destabilization of the medial meniscus) -induced osteoarthritic lesions in the knee joint of C57BL/6 mice (6 week), while overexpression and suppression effects of the SREBP-2 was separately delivered via adenovirus to the chondrocytes in vitroand knee joints in vivo in normal and OA mice fed with chow or high-fat diet in light of the pathogenic properties of SREBP-2. Results: 1 of 14 (7.14%) normal, 1 of 12 (8.33%) DMM-induced OA mice were increased SREBP-2 expression compared with 6 of 14 (42.85%) and 9 of 12 (75.00%) littermates treated high-fat diet as noted by immunohistostaining and real-time polymerase chain reaction (RT-PCR) assays (up to 6.01- and 9.03- fold difference, respectively, p ≤ 0.010), while expression of SREBP-2 related genes (SCAP, S1P, and HMGCR) was measured in 2 of 14 (14.29%), 1 of 14 (7.14%), and 2 of 14 (14.29%) normal controls, 1 of 12 (8.33%), 1 of 12 (8.33%), and 2 of 12 (16.67%) DMM-induced OA mice, and 6 of 14 (42.86%), 6 of 14 (42.86%), 5 of 14 (35.71%) and 7 of 12 (58.33%), 10 of 12 (83.33%), 10 of 12 (83.33%) to their corresponding mouse models as determined by immunohistostaining and RT-PCR assays (up to 3.00-, 6.00-, 2.50-, 7.00-, 10.00-, and 5.00- fold difference for SCAP, S1P and HMGCR, respectively, p ≤ 0.010). Overexpression of the SREBP-2 downregulated the expression of extracellular matrix markers of normal cartilage (type II collagen and aggrecan), while enhanced the type X collagen (hypertrophy) and type I collagen (osteoblastic matrix marker) both in chondrocytes in vitro and cartilage in vivo in mice, and findings in the contrary with the suppression of SREBP-2 were characterized. Conclusions: These findings demonstrate that expression of SREBP-2 and its related genes is higher in knee cartilage of high-fat diet-induced obese mice models, and suppression of SREBP-2 might contribute bio-protective effects upon chondrocytes.

Chondrocyte specific expression of CCN2 does not modify osteoarthritis development in mice

Purpose: CCN2 is a matricellular protein which has been shown to be heavily involved in several complex biological processes including angiogenesis, fibrosis, and chondrogenesis. CCN2 is known to be expressed in both healthy and osteoarthritic cartilage, and involved in the production of the major cartilage matrix proteins; aggrecan and collagen type II. CCN2 null mice have been reported to exhibit a range of skeletal dysmorphisms, highlighting the importance of CCN2 in regulating matrix formation and turnover. The aim of this study was to determine the function of CCN2 in chondrocytes postnatally, in models of trauma-induced osteoarthritis (OA). Methods: Three double transgenic mouse models were generated; two inducible CCN2 knockout (KO) lines and one inducible CCN2 overexpressing (O/E) line. Both CCN2 KO lines contained Aggrecan CreERT2 enhancers which enabled the deletion of CCN2 from different populations of chondrocytes, whilst the O/E line contained an UbcCCN2-IRES-LacZ transgene enabling CCN2 O/E in all chondrocytes. CCN2 deletion and overexpression was induced following tamoxifen treatment in males aged 8 weeks. OA was induced either through surgical injury (transection of the medial meniscus and medial menisco-tibial ligament), or non-invasively by applying a controlled loading regimen to the tibio-femoral joint at 10 weeks of age. Knee joints were harvested and fixed, scanned with μCT, and processed for histology. Sections were stained with Toluidine Blue and scored for articular cartilage degeneration using the OARSI grading system. Results: In the surgical model of OA, cartilage degeneration was most severe on the medial side of the joint, however no significant differences were observed between lesion severity in wildtype (WT) and KO at any of the time-points analysed (2, 4, and, 8 weeks post-surgery). In the non-invasive model of OA lesion severity was most severe on the lateral femur in both the KO and O/E lines. As with the surgical model, no differences in lesion severity were observed between WT / KO and WT / O/E when analysed 6 weeks post-loading. μCT analysis of trabecular bone BV/TV and joint space in both models showed no effect of CCN2 KO and O/E between WT and experimental animals. Conclusions: CCN2 did not appear to play a protective role in the development of OA irrespective of whether the damage was induced surgically or non-invasively. The progression and severity of OA in both models, at all time-points, suggests the expression of CCN2 specifically in chondrocytes is not enough to protect articular cartilage from the degeneration associated with trauma-induced OA.

Histological Study of the Anterior Cruciate Ligament in Patients with Osteoarthritis

The anterior cruciate ligament (ACL) plays a crucial role in preventing the anterior translocation and medial rotation of the tibia against the femur. The normal histological composition of the ACL has been described as 99% dense regular connective tissue (DRCT), 0.9% loose connective tissue, and 0.1% vasculature with no nerves or adipose tissue present. Previous data on ACL structure in patients with knee osteoarthritis (OA) indicate that the ligament undergoes degenerative changes in OA patients. The objective of the current study was to evaluate the details of histological changes in the ACLs of patients with clinically diagnosed OA. The study was approved by the local institutional review board. The ACLs from six patients undergoing total knee replacement because of OA (OA group) and eleven normal ACLs from the Kirksville College of Osteopathic Medicine anatomy lab (control group) were collected. Demographic data, medical history, and Outerbridge scores were also collected. The average Outerbridge score in the OA group was 3.6 on a scale of 0–4. Nonconsecutive 10 μm longitudinal tissue slices of ACLs stained with hematoxylin and eosin were analyzed for tissue composition and amount of blood vessels. To account for possible differences in tissue composition across the ligament, the full length and full thickness of each ACL were analyzed using nine sections from each ACL, from which the data were averaged. ImageJ software was used to calculate percentages for total area and areas of DRCT, degenerative tissue, and vasculature. Generalized linear mixed models were used to compare tissue composition and relative amount of blood vessels in the OA and control groups. There was no significant difference in tissue composition or vasculature between age groups (both P&gt;.37). The major difference in the histological structure of the ACL between the two groups was the proportion of DRCT to non‐DRCT, which was significantly smaller in the OA group than the control group (OA, 50%; control, 96%; P&lt;.001). The non‐DRCT included degenerative connective tissue and fibrocartilage. The ratio of blood vessels to area was greater in the OA group than the control group (OA, 0.12 vessels/mm2; control, 0.02 vessels/mm2; P=.01). These results indicate that the inflammatory processes in the knee contributing to OA lesions cause changes in the composition of the ACL that lead to destruction of collagen bundles, increased vascularization, edema, and formation of fibrocartilage‐like tissue inside the ligament. Thus, the ACLs from patients with severe OA undergo marked histological changes, making them less suitable for ligament‐retaining total knee arthroplasty.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Modular Lattice Constructs for Biological Joint Resurfacing.

The repair of large articular cartilage lesions is still a major challenge. In particular, the fixation of the grafts to the subchondral bone plate represents an unresolved problem. In this work, we present a completely novel concept based on a modular lattice, combining building blocks of different ceramic materials, anchoring pins and space for cell-loaded hydrogels or other scaffold materials. This concept targets not only circumscribed cartilage defects but also large osteoarthritic lesions. It spans the bridge between cell therapy and artificial joint arthroplasty, and thus is of significant medical and socioeconomic impact.

Correlation Between Medial Meniscal Extrusion Determined by Dynamic Ultrasound and Magnetic Resonance Imaging Findings of Medial-Type Knee Osteoarthritis in Patients With Knee Pain.

The aim of our study was to investigate the relationship between medial meniscal extrusion (MME) determined by dynamic ultrasound (US) and magnetic resonance imaging findings of medial-type knee osteoarthritis (OA). Single knees of 102 patients with knee pain were assessed by radiography, dynamic US, and magnetic resonance imaging. All knee radiographs were interpreted and grouped according to the Kellgren-Lawrence (KL) scale. Medial meniscal extrusion in non-weight-bearing and weight-bearing positions and the difference of these values (ΔMME) were measured by dynamic US. The medial tibiofemoral compartments of all knees were evaluated and grouped according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Mean values of non-weight-bearing MME, weight-bearing MME, and ΔMME ± standard deviations for groups formed according to the KL scale and WORMS system were compared. We demonstrated that different from non-weight-bearing MME, weight-bearing MME was significantly correlated with not only high grades but also lower grades of cartilage damage and subchondral bone marrow lesions in medial-type knee OA. Although the difference in non-weight-bearing MME between cartilage status groups 1 and 2 was not significant (P = .071), there were significant differences in of weight-bearing MME between groups 1 and 2, between groups 2 and 3, and between groups 3 and group 4 (P = .003, .002, and .032, respectively). We found statistically significant associations between MME values and the severity of the OA findings according to both the KL scale and WORMS system. We offer dynamic US as an initial tool for the diagnosis and a screening method to estimate the severity of knee OA.

OMERACT agreement and reliability study of ultrasonographic elementary lesions in osteoarthritis of the foot

ObjectiveTo evaluate the level of agreement on ultrasonographic (US) lesions among highly experienced sonographers as well as the intraobserver and interobserver reliability of inflammatory and structural US lesions in patients...

OMERACT Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) Assessment in Longitudinal Study.

To assess reliability, feasibility, and responsiveness of Hip Inflammation Magnetic resonance imaging Scoring System (HIMRISS) for bone marrow lesions (BML) in hip osteoarthritis (OA). HIMRISS was scored by 8 readers in 360 hips of 90 patients imaged pre/post-hip steroid injection. Pre-scoring, new readers trained online to achieve intraclass correlation coefficient (ICC) > 0.80 versus experts. HIMRISS reliability was excellent for BML status (ICC 0.83-0.92). Despite small changes post-injection, reliability of BML change scores was high in femur (0.76-0.81) and moderate in acetabulum (0.42-0.56). HIMRISS should be a priority for further assessment of hip BML in OA, and evaluated for use in other arthropathies.

Acromioclavicular joint : The "forgotten" joint

Besides osteoarthritic changes, traumatic and posttraumatic lesions are the most frequent alterations of the acromioclavicular (AC) joint. The Rockwood classification is used to describe posttraumatic lesions. The most important screening modality is anteroposterior x‑ray imaging, preferably with weight bearing and side to side comparison. Magnetic resonance imaging (MRI) without weight bearing is superior to x‑rays in analyzing and classifying AC joint dislocations. Postoperative imaging and assessment of arthritic alterations are usually carried out using x‑ray images and MRI is used as an additional examination modality. Sonography is only of limited value. Multidetector computed tomography (MDCT) is usually not used as aprimary imaging modality for the AC joint; however, it can be analyzed simultaneously whenever the shoulder joint is being investigated with MDCT.

Bone Density and Texture from Minimally Post-Processed Knee Radiographs in Subjects with Knee Osteoarthritis

Plain radiography is the most common modality to assess the stage of osteoarthritis. Our aims were to assess the relationship of radiography-based bone density and texture between radiographs with minimal and clinical post-processing, and to compare the differences in bone characteristics between controls and subjects with knee osteoarthritis or medial tibial bone marrow lesions (BMLs). Tibial bone density and texture was evaluated from radiographs with both minimal and clinical post-processing in 109 subjects with and without osteoarthritis. Bone texture was evaluated using fractal signature analysis. Significant correlations (p < 0.001) were found in all regions (between 0.94 and 0.97) for calibrated bone density between radiographs with minimal and clinical post-processing. Correlations varied between 0.51 and 0.97 (p < 0.001) for FDVer texture parameter and between − 0.10 and 0.97 for FDHor. Bone density and texture were different (p < 0.05) between controls and subjects with osteoarthritis or BMLs mainly in medial tibial regions. When classifying healthy and osteoarthritic subjects using a machine learning-based elastic net model with bone characteristics, area under the receiver operating characteristics (ROCAUC) curve was 0.77. For classifying controls and subjects with BMLs, ROCAUC was 0.85. In conclusion, differences in bone density and texture can be assessed from knee radiographs when using minimal post-processing.

The commercial pig as a model of spontaneously-occurring osteoarthritis

BackgroundPreclinical osteoarthritis models where damage occurs spontaneously may better reflect the initiation and development of human osteoarthritis. The aim was to assess the commercial pig as a model of spontaneous osteoarthritis development by examining pain-associated behaviour, joint cartilage integrity, as well as the use of porcine cartilage explants and isolated chondrocytes and osteoblasts for ex vivo and in vitro studies.MethodsFemale pigs (Large white x Landrace x Duroc) were examined at different ages from 6 weeks to 3–4 years old. Lameness was assessed as a marker of pain-associated behaviour. Femorotibial joint cartilage integrity was determined by chondropathy scoring and histological staining of proteoglycan. IL-6 production and proteoglycan degradation was assessed in cartilage explants and primary porcine chondrocytes by ELISA and DMMB assay. Primary porcine osteoblasts from damaged and non-damaged joints, as determined by chondropathy scoring, were assessed for mineralisation, proliferative and mitochondrial function as a marker of metabolic capacity.ResultsPigs aged 80 weeks and older exhibited lameness. Osteoarthritic lesions in femoral condyle and tibial plateau cartilage were apparent from 40 weeks and increased in severity with age up to 3–4 years old. Cartilage from damaged joints exhibited proteoglycan loss, which positively correlated with chondropathy score. Stimulation of porcine cartilage explants and primary chondrocytes with either IL-1β or visfatin induced IL-6 production and proteoglycan degradation. Primary porcine osteoblasts from damaged joints exhibited reduced proliferative, mineralisation, and metabolic capacity.ConclusionIn conclusion, the commercial pig represents an alternative model of spontaneous osteoarthritis and an excellent source of tissue for in vitro and ex vivo studies.