Search Results (5)

Osteoarthritis (OA), the most common form of arthritis, affects the whole synovial joint. Post-traumatic osteoarthritis (PTOA) is an important subtype of OA which develops after joint injury. The anti-PTOA effects of iontophoretic liposome-encapsulated strontium ranelate (L-SR) combined with low-intensity pulsed ultrasound (LIPUS) were examined by a culture of human OA chondrocytes (HOACs) in alginate beads and verified on an anterior cruciate ligament transection PTOA rat model. The aim of this study is to evaluate and establish an anti-PTOA therapy combined with L-SR, transdermal iontophoresis, and LIPUS. Treatment with 10⁻⁴ M L-SR with LIPUS-enhanced type II collagen and glycosaminoglycans (GAGs) as L-SR with LIPUS reduced the MMP-13, IL-1β, and TNF-α in HOACs. Iontophoretic L-SR at 15 mg with LIPUS increased the weight bearing, exercise endurance, GAG density, and type II collagen intensity, while L-SR with or without LIPUS further decreased MMP13 and proinflammatory cytokines in vivo. The RBC, WBC, and serum biochemistry values were not significantly affected by the treatments. Liposome encapsulation and iontophoresis reinforce the anti-PTOA effects of SR and the addictive LIPUS further improves weight-bearing and endurance performance in the rats with PTOA. Thus, iontophoretic L-SR with LIPUS could be a potential therapy for PTOA. Full article

Post-traumatic osteoarthritis (PTOA) is a common cause of lameness in the horse. There is no cure, therefore treatments are aimed at reducing pain and improving the joint environment by modifying inflammatory pathways or by viscosupplementation. Here, we report the safety and efficacy of the biolubricant (poly(2-methacryloyloxyethyl phosphorylcholine; pMPC) to mitigate the physical, gross, histological, and biochemical effects of arthritis. We created an osteochondral fragment in the middle carpal joint of one limb in 16 horses to induce PTOA; the contralateral limb served as a sham-operated joint. Two weeks postoperative, half (n = 8) of the horses received a single injection of pMPC in the PTOA joint, while the other half received saline. All sham-operated joints (n = 16) received saline. We conducted clinical evaluations weekly while synovial fluid biomarkers were measured biweekly during the 70-day study period. Subsequently, we performed postmortem gross and histologic analyses. Horses in which PTOA joints were treated with pMPC exhibited mild increases in clinical data, including lameness, effusion, and flexion scores. Similarly, synovial cell count, total protein, and prostaglandin E₂ values were higher for pMPC-treated joints. Radiographic changes included significantly higher osteophyte scores in pMPC-treated joints at the terminal timepoint. The biolubricant may demonstrate some chondroprotective effects with lower total erosion scores and higher cartilage glycosaminoglycan content. In summary, when pMPC is administered to PTOA joints, the biolubricant induces a mild inflammatory response but may offer some chondroprotective effects in horses. Full article

Background: Senescence, a characteristic of cellular aging and inflammation, has been linked to the acceleration of osteoarthritis. The purpose of this study is to prospectively identify, measure, and compare senescent profiles in synovial fluid and peripheral blood in patients with an acute knee injury within 48 h. Methods: Seven subjects, aged 18–60 years, with an acute ACL tear with effusion were prospectively enrolled. Synovial fluid and peripheral blood samples were collected and analyzed by flow cytometry, using senescent markers C12FDG and CD87. The senescent versus pro-regenerative phenotype was probed at a gene and protein level using qRT-PCR and multiplex immunoassays. Results: C₁₂FDG and CD87 positive senescent cells were detected in the synovial fluid and peripheral blood of all patients. Pro-inflammatory IL-1β gene expression measured in synovial fluid was significantly higher (p = 0.0156) than systemic/blood expression. Senescent-associated factor MMP-3 and regenerative factor TIMP-2 were significantly higher in synovial fluid compared to blood serum. Senescent-associated factor MMP-9 and regenerative factor TGFβ-2 were significantly elevated in serum compared to synovial fluid. Correlation analysis revealed that C12FDG⁺⁺/CD87⁺⁺ senescent cells in synovial fluid positively correlated with age-related growth-regulated-oncogene (ρ = 1.00, p < 0.001), IFNγ (ρ = 1.00, p < 0.001), IL-8 (ρ = 0.90, p = 0.0374), and gene marker p16 (ρ = 0.83, p = 0.0416). Conclusions: There is an abundance of senescent cells locally and systemically after an acute ACL tear without a significant difference between those present in peripheral blood compared to synovial fluid. This preliminary data may have a role in identifying strategies to modify the acute environment within the synovial fluid, either at the time of acute ligament injury or reconstruction surgery. Full article

The pathophysiology of post-traumatic arthritis (PTOA) is not fully understood. This study used non-invasive repetitive mechanical loading (ML) mouse models to study biochemical, biomechanical, and pain-related behavioral changes induced in mice. Mouse models reflected the effects of the early stages of PTOA in humans. For the PTOA model, cyclic comprehensive loading (9N) was applied to each mouse’s left knee joint. ML-induced biochemical and molecular changes were analyzed after loading completion. Cartilage samples were examined using gene expression analysis. Tissue sections were used in subsequent OA severity scoring. Biomechanical features and pain-related behavior were studied after 24 h and three weeks post-ML sessions to examine the development of PTOA. The loaded left knee joint showed a greater ROS/RNS signal than the right knee, which was not loaded. There was a significant increase in cartilage damage and MMP activity in the mechanically loaded joints relative to non-loaded control knee joints. Similarly, we found a difference in the viscoelastic tangent, which highlights significant changes in mechanical properties. Biochemical analyses revealed significant increases in total NO, caspase-3 activity, H₂O₂, and PGE2 levels. Gene expression analysis highlighted increased catabolism (MMP-13, IL-1β, TNF-α) with a concomitant decrease in anabolism (ACAN, COL2A1). Histopathology scores clearly indicated increases in OA progression and synovitis. The gait pattern was significantly altered, suggesting signs of joint damage. This study showed that biomechanical, biochemical, and behavioral characteristics of the murine PTOA groups are significantly different from the control group. These results confirm that the current mouse model can be considered for translational PTOA studies. Full article

Aging and injury are two major risk factors for osteoarthritis (OA). Yet, very little is known about how aging and injury interact and contribute to OA pathogenesis. In the present study, we examined age- and injury-related molecular changes in mouse knee joints that could contribute to OA. Using RNA-seq, first we profiled the knee joint transcriptome of 10-week-old, 62-week-old, and 95-week-old mice and found that the expression of several inflammatory-response related genes increased as a result of aging, whereas the expression of several genes involved in cartilage metabolism decreased with age. To determine how aging impacts post-traumatic arthritis (PTOA) development, the right knee joints of 10-week-old and 62-week-old mice were injured using a non-invasive tibial compression injury model and injury-induced structural and molecular changes were assessed. At six-week post-injury, 62-week-old mice displayed significantly more cartilage degeneration and osteophyte formation compared with young mice. Although both age groups elicited similar transcriptional responses to injury, 62-week-old mice had higher activation of inflammatory cytokines than 10-week-old mice, whereas cartilage/bone metabolism genes had higher expression in 10-week-old mice, suggesting that the differential expression of these genes might contribute to the differences in PTOA severity observed between these age groups. Full article