Partial meniscectomies, a common treatment for meniscal tears, unfortunately cause osteoarthritis (OA) of the underlying cartilage. Finite element modeling has shown increases in compressive strains from 10% in an intact meniscus to 20% in menisci from which 30-60% tissue is removed. Cells within the meniscus may contribute to joint degeneration by producing catabolic molecules such as nitric oxide (NO) and interleukin 1 (IL-1) in response to changes in their mechanical environment brought on by changes in meniscal loading. Additionally, elliptical cells in superior regions are more sensitive to changes in mechanical loading compared to spherical cells in deeper regions. This study tests the hypotheses that IL-1 upregulates iNOS expression at abnormally high levels of compression (~20%), that upregulation is caused by increased mechanical loading on cells and that different cell populations experience different levels of cellular loading due to their different morphologies, positions and sizes. Porcine meniscal explants were dynamically compressed for 2hours at 1Hz to simulate physiological loading (5-10% strain) and pathological loading (0% and 15-20% strains). Relative changes in gene expression of inducible nitric oxide synthase (iNOS), which produces NO and subsequent changes in the concentration of NO itself were measured while blocking the action of IL1. Elliptical and circular cells were modeled within an explant to analyze the changes in mechanical parameters such as cellular stresses, strains and fluid velocities at increasing strains. Results showed that iNOS gene expression and NO release into the surrounding media increased at 20% compressive strain from a minimum at 10%. Increased iNOS expression was eliminated by blocking IL-1. Finite element modeling showed that elliptical (superior) cells may be more sensitive to mechanical loading due to their morphology. The greatest difference between circular and elliptical cells was seen in cellular stresses suggesting stresses may be an important regulator of compression related increases in iNOS gene expression. In conclusion, meniscectomies which reduce the surface area of the meniscus by 30% to 60% increase cellular loading and subsequently increase iNOS gene expression and NO concentrations via an IL-1 dependant pathway which may lead to osteoarthritis by being detrimental to remaining meniscal tissue.