ROLE OF SKELETAL PARACRINE SIGNALS IN THE PROLIFERATION AND CHONDROGENIC DIFFERENTIATION OF INTERZONE CELLS

Articular cartilage in mammals has a limited intrinsic capacity to repair structural injuries and defects, a fact that contributes to the chronic and progressive nature of osteoarthritis. Current treatment modalities do not enable articular cartilage to achieve a complete and permanent restoration of normal structure and function with large or partial thickness lesions. In contrast to mammals, Mexican axolotl salamanders (Ambystoma mexicanum) have demonstrated the remarkable ability to spontaneously and completely repair even large joint cartilage lesions, an intrinsic healing process that involves interzone cells in the intraarticular space. Further, when interzone tissue is transplanted into critical sized diaphyseal defects, it forms an entirely new diarthrodial joint in these amphibians, demonstrating a multi-differentiation potential. Cellular and molecular mechanisms of this repair process, however, remain unclear. This thesis examined whether paracrine signals are an important variable in the interaction between interzone cells and the skeletal microenvironment. In vivo experiments in axolotl salamanders compared the outcomes of interzone tissue transplants placed in either a skeletal or non-skeletal site within the same individual. The hypothesis tested was that the interzone-mediated repair of skeletal defects is regulated by mechanisms that are localized to the skeletal microenvironment. Interzone cell proliferation and differentiation was only observed in skeletal transplant sites, suggesting that local signals from the skeletal microenvironment played a vital role in the interzone-mediated repair process. In a second series of experiments, paracrine regulation of the proliferation and chondrogenic differentiation of equine interzone cells was evaluated in an in vitro co-culture system. The results of cellular proliferation studies indicated a mitogenic effect of skeletal paracrine signals on interzone cells. Expression of cartilage biomarker genes, evaluated at both RNA and protein levels, were used to assess chondrogenic differentiation. The in vitro findings suggested that paracrine signals may have a role in the chondrogenic differentiation of interzone cells, but were not compelling. The response may have been limited by levels of paracrine factor accumulation achieved in the co-culture system used for these experiments. Taken together, however, the data support a model that paracrine factors from skeletal tissues are important regulators of interzone cell proliferation and differentiation. This knowledge advances the assessment of interzone cells as a potential cell-based therapy for the repair of articular cartilage injuries

Modeling and analysis of field-oriented control based permanent magnet synchronous motor drive system using fuzzy logic controller with speed response improvement

The permanent magnet synchronous motor (PMSM) acts as an electrical motor mainly used in many diverse applications. The controlling of the PMSM drive is necessary due to frequent usage in various systems. The conventional proportional-integral-derivative (PID) controller’s drawbacks are overcome with fuzzy logic controller (FLC) and adopted in the PMSM drive system. In this manuscript, an efficient field-oriented control (FOC) based PMSM drive system using a fuzzy logic controller (FLC) is modeled to improve the speed and torque response of the PMSM. The PMSM drive system is modeled using abc to αβ and αβ to abc transformation, 2-level space vector pulse width modulation (SVPWM), AC to DC rectifier with an inverter, followed by PMSM drive, proportional integral (PI) controller along with FLC. The FLC’s improved fuzzy rule set is adopted to provide faster speed response, less % overshoot time, and minimal steady-state error of the PMSM drive system. The simulation results of speed response, torque response, speed error, and phase currents are analyzed. The FLC-based PMSM drive is compared with the conventional PID-based PMSM drive system with better improvements in performance metrics

Gene therapy approaches for equine osteoarthritis

With an intrinsically low ability for self-repair, articular cartilage injuries often progress to cartilage loss and joint degeneration resulting in osteoarthritis (OA). Osteoarthritis and the associated articular cartilage changes can be debilitating, resulting in lameness and functional disability both in human and equine patients. While articular cartilage damage plays a central role in the pathogenesis of OA, the contribution of other joint tissues to the pathogenesis of OA has increasingly been recognized thus prompting a whole organ approach for therapeutic strategies. Gene therapy methods have generated significant interest in OA therapy in recent years. These utilize viral or non-viral vectors to deliver therapeutic molecules directly into the joint space with the goal of reprogramming the cells' machinery to secrete high levels of the target protein at the site of injection. Several viral vector-based approaches have demonstrated successful gene transfer with persistent therapeutic levels of transgene expression in the equine joint. As an experimental model, horses represent the pathology of human OA more accurately compared to other animal models. The anatomical and biomechanical similarities between equine and human joints also allow for the use of similar imaging and diagnostic methods as used in humans. In addition, horses experience naturally occurring OA and undergo similar therapies as human patients and, therefore, are a clinically relevant patient population. Thus, further studies utilizing this equine model would not only help advance the field of human OA therapy but also benefit the clinical equine patients with naturally occurring joint disease. In this review, we discuss the advancements in gene therapeutic approaches for the treatment of OA with the horse as a relevant patient population as well as an effective and commonly utilized species as a translational model