The Updated Role of Ultrasound in the Assessment of Knee Osteoarthritis

Background Osteoarthritis (OA) of the knee is the most common form of knee arthritis and a leading cause of chronic disability. Objective The aim of the current study is to reassess the utility of the updated ultrasound in the patients with knee osteoarthritis and outline its clinical application. Patients and Methods The studied group included 36 patient 23females and 13 males with their ages ranged between 39 and 58 years (average age 44 years). The patients were referred to US examination fulfilling the ACR clinical criteria for knee OA after orthopedic and /or rheumatologist consultation. The study was performed in Radiodiagnosis department Ain Shams University Hospitals (20 patients ) and at one private center (16 patients). Results There was a discrepancy between the results obtained by clinical examination and those demonstrated by ultrasonography. Clinical examination detected 22 (61.1%) of our cases. Prevalence of US findings in our cases were femoral articular degeneration in 28 (77.7%) patients, Tibiofemoral osteophytes were seen in 26 patients (72.2%), knee effusion in 22 patients (61.1%),meniscal extrusion in 22 patients (61.1%) meniscal degeneration in 17 patients (47.2%) and synovial hypertrophy in 15patients (41.6%). Baker’s cysts were demonstrated in 14patients (38.8%) while pes anserine syndrome was demonstrated in 4 cases. Meniscal degeneration and meniscal extrusion were correlated significantly with femoral cartilage degeneration (P<.001). Although knee effusion did not correlate with advanced knee effusion did significantly (P > 0.05). Baker's cysts is statistically related to the presence and severity of mensical changes and also related to the degree of femoral articular cartilage degeneration. Conclusion US is a valuable technique that can assess soft tissue structures within the knee and their involvement in the osteoarthritic process .US enables in guiding and monitoring therapy through detection of knee structural damage.

POS0372 LORECIVIVINT (SM04690), AN INTRA-ARTICULAR, SMALL-MOLECULE CLK2/DYRK1A INHIBITOR THAT MODULATES THE WNT PATHWAY, AS A POTENTIAL TREATMENT FOR MENISCAL INJURIES

Background:Meniscal injuries are the most common pathology of the knee and are associated with pain, stiffness, and localized swelling. Meniscal damage is a frequent finding on MRI images of knee osteoarthritis (OA).1 Efforts to repair meniscal damage have been largely unsuccessful and do not prevent the progression of degenerative changes that lead to knee OA.2 The Wnt signaling pathway has been shown to be regulated during meniscal development,3 suggesting that manipulation of this pathway may influence the regenerative capacity of the meniscus. Lorecivivint (LOR; SM04690) is an intra-articular (IA), small-molecule CLK2/DYRK1A inhibitor that modulates the Wnt pathway.4Objectives:LOR was evaluated in preclinical studies to determine its protective and anabolic effects in ex vivo explants and in a rat model of chemically induced inflammatory meniscal degeneration.Methods:Effects of LOR (30 nM) on matrix metalloproteinase (MMP) expression in cultured rat menisci treated with IL-1B were measured by qRT-PCR. In vivo, LOR activity was evaluated in a rat model of monosodium iodoacetate (MIA) injection-induced inflammatory meniscal degeneration. A single IA injection of MIA was immediately followed by a single IA injection of LOR (0.3 ug) or vehicle. Knees were harvested on Days 1, 4, and 11 and menisci were isolated. Anti-inflammatory effects were evaluated by qRT-PCR for TNFA and IL6 expression. Meniscal protection was evaluated by qRT-PCR for MMPs and aggrecanase. Anabolic effects were evaluated by qRT-PCR for collagens.Results:In ex vivo meniscal explants, LOR inhibited expression of MMP1, MMP3, and MMP13 compared with DMSO (P<0.01). In vivo, LOR significantly decreased expression of MMPs and aggrecanase (P<0.05) and reduced expression of inflammatory cytokines TNFA and IL6 compared with vehicle in the rat model of inflammatory meniscal degeneration at Day 4 after MIA injection. Additionally, LOR increased expression of collagen types I, II, and III at Day 11 after MIA injection (Figure 1).Conclusion:LOR exhibited protective effects in the meniscus ex vivo and in vivo by reducing catabolic enzyme expression compared with control. Anti-inflammatory effects of LOR were demonstrated by inhibition of inflammatory cytokine expression. Compared with vehicle, LOR increased collagen expression in vivo, indicating potential meniscal anabolic effects. These data support further investigation of LOR as a potential structure-modifying treatment for meniscal injuries.References:[1]Englund M, et al. Rheum Dis Clin North Am. 2009.[2]Collins JE, et al. Arthritis Care Res (Hoboken). 2019.[3]Pazin DE, et al. Dev Dyn. 2012.[4]Deshmukh V, et al. Osteoarthr Cartil. 2019.Disclosure of Interests:Tim Seo Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Vishal Deshmukh Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Yusuf Yazici Shareholder of: Samumed, LLC, Employee of: Samumed, LLC

An animal model study on the gene expression profile of meniscal degeneration

Meniscal degeneration is a very common condition in elderly individuals, but the underlying mechanisms of its occurrence are not completely clear. This study examines the molecular mechanisms of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of seven Wuzhishan mini-pigs were resected (meniscal degeneration group), and the left rear legs were sham-operated (control group). After 6 months, samples were taken for gene chip analysis, including differentially expressed gene (DEG) analysis, gene ontology (GO) analysis, clustering analysis, and pathway analysis. The selected 12 DEGs were validated by real time reverse transcription-polymerase chain reaction (RT-PCR). The two groups showed specific and highly clustered DEGs. A total of 893 DEGs were found, in which 537 are upregulated, and 356 are downregulated. The GO analysis showed that the significantly affected biological processes include nitric oxide metabolic process, male sex differentiation, and mesenchymal morphogenesis, the significantly affected cellular components include the endoplasmic reticulum membrane, and the significantly affected molecular functions include transition metal ion binding and iron ion binding. The pathway analysis showed that the significantly affected pathways include type II diabetes mellitus, inflammatory mediator regulation of TRP channels, and AMPK signaling pathway. The results of RT-PCR indicate that the microarray data accurately reflects the gene expression patterns. These findings indicate that several molecular mechanisms are involved in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and provide molecular therapeutic targets in the future.

Traumatic Meniscal Tears Are Associated With Meniscal Degeneration

Background: Meniscal tears are traditionally classified into traumatic versus degenerative tears. Although this classification plays a major role in clinical decision making, no consensus exists on the exact definition of a traumatic or degenerative tear, and the histopathological basis for this classification is unclear. Purpose: To assess the histological degree of meniscal degeneration in patients with a traumatic meniscal tear, as compared with intact meniscal tissue and osteoarthritic meniscal tissue. Study Design: Descriptive laboratory study. Methods: Traumatically torn meniscal tissue was collected during arthroscopic partial meniscectomy. As a control group, intact meniscal tissue was used from transfemoral amputations or direct postmortem dissections. Meniscal tissue from osteoarthritic knees was obtained during total knee replacement surgery. Meniscal tissue was processed, stained, and histologically analyzed with the Pauli scoring system (range, 0-18), comprising the subdomains surface integrity, cellularity, collagen organization, and matrix staining. Scoring was performed by 2 independent observers, blinded to condition, region, and patient data of the meniscus. Results: The traumatic meniscal tear group contained 43 patients (34 men; median age, 29 years; median body mass index [BMI], 24 kg/m2); the intact meniscal tissue group, 8 patients (3 men; median age, 58 years; median BMI, 30 kg/m2); and the osteoarthritic group, 14 patients (4 men; median age, 66 years; median BMI, 28 kg/m2). After adjustment for sex, age, and BMI, patients with a traumatic meniscal tear had a significantly higher histological score than patients with intact meniscal tissue (2.7-point difference; P = .035). Histological score between the traumatic and osteoarthritic groups was not different. Conclusion: Traumatically torn menisci possess a higher degree of degeneration than intact menisci. Our results suggest that patients with a traumatic meniscal tear may already have had a certain degree of meniscal degeneration. These findings potentially challenge the classic view of traumatic versus degenerative meniscal tears. Clinical Relevance: Our findings provide a better understanding of the tissue condition of a torn meniscus. This knowledge may help clinicians decide on choice of treatment and may lead to new perspectives to prevent knee osteoarthritis in patients with a torn meniscus.