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Objective Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation. Design rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats ( n = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP ( n = 10) or phosphate buffered saline (PBS; n = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test. Results Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration ( P = 0.042) and decreased mechanical allodynia ( P < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP. Conclusion rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.

Chondroprotection in Models of Cartilage Injury by Raising the Temperature and Osmolarity of Irrigation Solutions Noha M. Eltawil, Saima Ahmed, Luke H. Chan, A. Hamish R. W. Simpson, Andrew C. Hall First Published January 30, 2017 research-article PDF download for Chondroprotection in Models of Cartilage Injury by Raising the Temperature and Osmolarity of Irrigation Solutions Article Information SAGE Choice Open Access Creative Commons Attribution 3.0 License Abstract Objectives During arthroscopic or open joint surgery, articular cartilage may be subjected to mechanical insults by accident or design. These may lead to chondrocyte death, cartilage breakdown and posttraumatic osteoarthritis. We have shown that increasing osmolarity of routinely used normal saline protected chondrocytes against injuries that may occur during orthopedic surgery. Often several liters of irrigation fluid are used during an orthopedic procedure, which is usually kept at room temperature, but is sometimes chilled. Here, we compared the effect of normal and hyperosmolar saline solution at different temperatures on chondrocyte viability following cartilage injury using in vitro and in vivo models of scalpel-induced injury. Design Cartilage injury was induced in bovine osteochondral explants and the patellar groove of rats in vivo by a single pass of a scalpel blade in the presence of normal saline (300 mOsm) or hyperosmolar saline solution (600 mOsm, sucrose addition) at 4°C, 21°C, or 37°C. Chondrocytes were fluorescently labeled and visualized by confocal microscopy to assess cell death. Results Hyperosmolar saline reduced scalpel-induced chondrocyte death in both bovine and rat cartilage by ~50% at all temperatures studied (4°C, 21°C, 37°C; P < 0.05). Raising temperature of both irrigation solutions to 37°C reduced scalpel-induced cell death (P < 0.05). Conclusions Increasing the osmolarity of normal saline and raising the temperature of the irrigation solutions to 37°C reduced chondrocyte death associated with scalpel-induced injury in both in vitro and in vivo cartilage injury models. A hyperosmolar saline irrigation solution at 37°C may protect cartilage by decreasing the risk of chondrocyte death during mechanical injury.

Objective: Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. Results: A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Conclusion: Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

Joint injuries are common, especially among young adults aged 18 to 44 years. They are accompanied by a cascade of events that increase the risk of posttraumatic osteoarthritis (PTOA). Therefore, understanding of biological responses that predispose to PTOA should help in determining treatment modalities to delay and/or prevent the onset and progression of the disease. The vast majority of the literature pointed to chondrocyte death and apoptosis, inflammation and matrix damage/fragmentation being the earliest events that follow joint trauma. Together these events lead to the development of osteoarthritis-like focal cartilage lesions that if untreated have a tendency to expand and progress to fully developed disease. Currently, the only treatments available for joint trauma are surgical interventions. Experimental biologic approaches involve engineering of cartilage with the use of cells (stem cells or chondrocytes), juvenile or adult cartilage pieces, scaffolds, and various polymeric matrices. The major challenge for all of them is regeneration of normal functional mature hyaline cartilage that can sustain the load, resist compression, and most important, integrate with the host tissue. If the tissue is spontaneously repaired it fails to reproduce original structure and function and thus, may be more susceptible to re-injury. Thus, there is a critical need to develop novel molecular mechanism-based therapeutic approaches to biologic chondral and/or osteochondral repair. The focus of this review is on the earliest molecular and cellular manifestations of injury that can be grouped based on the following therapeutic options for PTOA: chondroprotection, anti-inflammatory, matrix protection, and matrix remodeling/matrix synthesis.