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P&F Grant Awards

Year 5


Grant # 9

Study of Early Responses in Knee Joint Following Compressive Tibial Loading in Genetic Mouse Strains

PI: M. Farooq Rai, Ph.D.,

 

Specific Aims

This proposal seeks to answer a critical question in osteoarthritis (OA) research: is the susceptibility to posttraumatic OA (PTOA) functionally related to susceptibility to injurious compressive loading in a non-invasive model of knee joint trauma? Here, we aim to utilize a novel non-invasive compressive tibial loading model in genetic mouse strains to understand the short- and long-term consequences of injury on articular cartilage, bone and synovium from a genetic standpoint. In addition, we will get mechanistic insights into the early molecular differences between the two strains towards understanding the pathophysiology of loading on chondrocyte apoptosis, matrix distribution and synovial cell proliferation. To achieve these targets, this proposal has two specific aims: Specific Aim 1. Determine the congruence in phenotypic differences in articular cartilage, synovium and bone following impact loading on the joint in genetic mouse strains. Hypothesis 1: The strain protected from PTOA has ability to withstand injurious compressive loading. Rationale: Although the relationship between PTOA and impact of compressive loading in genetic mouse strains is unknown, we assume that a strain that is protected from developing PTOA is able to better withstand the impact of injurious loading as will be determined by changes in cartilage, synovium and bone. Specific Aim 2. Test the effects of compressive loading on chondrocyte apoptosis, matrix distribution and synovial cell proliferation across strains. Hypothesis 2: Compressive loading modulates chondrocyte apoptosis, matrix distribution and synovial cell proliferation in the knee joint tissues. Rationale: Using C57BL/6J mice, we have observed that various loading regimens induced chondrocyte apoptosis and cartilage matrix degradation along with disruption of collagen fibril arrangement. We would study these changes in LGXSM-6 and LGXSM-33 strains to stratify the differences in response to compressive loading.