Browsing by Author "Ren, Guomin"

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    Inflammatory Profiling in Early Osteoarthritis
    (2018-09-20) Ren, Guomin; Krawetz, Roman J.; Emery, Carolyn A.; De Koning, A. P. Jason
    Osteoarthritis (OA) is one of the most common chronic diseases worldwide which can lead to disability. There is a desperate need for the efficient and reliable detection of OA at the early stage when patients are likely to benefit most from disease interventions. It has been shown in previous studies that inflammation plays important roles in cartilage degeneration, synovitis, remodeling of the subchondral bone and pain. The purpose of this thesis was to determine if a panel of inflammatory cytokines were distinct within individuals with pre-radiographic OA and/or an increased risk of developing OA. Serum inflammatory profiles were analyzed within a number of patient cohorts [i.e., radiographic OA patients (hip and knee), youth with a history of intra-articular knee injury, corresponding controls]; and it was found that inflammatory profiles were distinct between knee vs. hip OA patients. Additionally, a computation method was developed which identified a coordinated change in cytokine profiles in the youth knee injury cohort. This computational methodology highlighted a number of candidate biomarkers that contributed to this observed difference, including C-C motif chemokine 22 (CCL22)/macrophage derived chemokine (MDC) which was selected for further study. In a pre-clinical rat OA model, it was found that CCL22 plays a functional role in chondrocyte apoptosis and cartilage degeneration. Further, it was found that CCL22 treated synovial fibroblasts demonstrated altered expression of inflammatory factors. These results suggested that CCL22 may be a biomarker and potential drug target in early OA. These results also suggested that CCL22 may be associated with OA pain, yet this was not examined directly and an in vivo model where CCL22 expression could be regulated would be required to test this hypothesis. While it was observed that CCL22 is expressed in damaged cartilage and acts on human chondrocytes and synovial fibroblasts, additional studies are required to determine how CCL22 triggered these changes in synovial fibroblasts as these results suggest this is CCR4 independent. Furthermore, it would be essential to validate these findings in an independent cohort to examine the sensitivity and/or specificity of CCL22 as an early OA biomarker.
  • Thumbnail Image
    ItemOpen Access
    Inflammatory Profiling in Early Osteoarthritis
    (2018-09-20) Ren, Guomin; Krawetz, Roman J.; Emery, Carolyn A.; De Koning, A. P. Jason
    Osteoarthritis (OA) is one of the most common chronic diseases worldwide which can lead to disability. There is a desperate need for the efficient and reliable detection of OA at the early stage when patients are likely to benefit most from disease interventions. It has been shown in previous studies that inflammation plays important roles in cartilage degeneration, synovitis, remodeling of the subchondral bone and pain. The purpose of this thesis was to determine if a panel of inflammatory cytokines were distinct within individuals with pre-radiographic OA and/or an increased risk of developing OA. Serum inflammatory profiles were analyzed within a number of patient cohorts [i.e., radiographic OA patients (hip and knee), youth with a history of intra-articular knee injury, corresponding controls]; and it was found that inflammatory profiles were distinct between knee vs. hip OA patients. Additionally, a computation method was developed which identified a coordinated change in cytokine profiles in the youth knee injury cohort. This computational methodology highlighted a number of candidate biomarkers that contributed to this observed difference, including C-C motif chemokine 22 (CCL22)/macrophage derived chemokine (MDC) which was selected for further study. In a pre-clinical rat OA model, it was found that CCL22 plays a functional role in chondrocyte apoptosis and cartilage degeneration. Further, it was found that CCL22 treated synovial fibroblasts demonstrated altered expression of inflammatory factors. These results suggested that CCL22 may be a biomarker and potential drug target in early OA. These results also suggested that CCL22 may be associated with OA pain, yet this was not examined directly and an in vivo model where CCL22 expression could be regulated would be required to test this hypothesis. While it was observed that CCL22 is expressed in damaged cartilage and acts on human chondrocytes and synovial fibroblasts, additional studies are required to determine how CCL22 triggered these changes in synovial fibroblasts as these results suggest this is CCR4 independent. Furthermore, it would be essential to validate these findings in an independent cohort to examine the sensitivity and/or specificity of CCL22 as an early OA biomarker.
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    ItemOpen Access
    Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain
    (2018-02-05) Ren, Guomin; Lutz, Ian; Railton, Pamela; Wiley, J. Preston; McAllister, Jenelle; Powell, James; Krawetz, Roman J
    Abstract Background Inflammation is associated with the onset and progression of osteoarthritis in multiple joints. It is well known that mechanical properties differ between different joints, however, it remains unknown if the inflammatory process is similar/distinct in patients with hip vs. knee OA. Without complete understanding of the role of any specific cytokine in the inflammatory process, understanding the ‘profile’ of inflammation in a given patient population is an essential starting point. The aim of this study was to identify serum cytokine profiles in hip Osteoarthritis (OA), and investigate the association between cytokine concentrations and clinical measurements within this patient population and compare these findings to knee OA and healthy control cohorts. Methods In total, 250 serum samples (100 knee OA, 50 hip OA and 100 control) and 37 synovial fluid samples (8 knee OA, 14 hip OA and 15 control) were analyzed using a multiplex ELISA based approach. Synovial biopsies were also obtained and examined for specific cytokines. Pain, physical function and activity within the hip OA cohort were examined using the HOOS, SF-36, HHS and UCLA outcome measures. Results The three cohorts showed distinct serum cytokine profiles. EGF, FGF2, MCP3, MIP1α, and IL8 were differentially expressed between hip and knee OA cohorts; while FGF2, GRO, IL8, MCP1, and VEGF were differentially expressed between hip OA and control cohorts. Eotaxin, GRO, MCP1, MIP1β, VEGF were differentially expressed between knee OA and control cohorts. EGF, IL8, MCP1, MIP1β were differentially expressed in synovial fluid from a sub-set of patients from each cohort. Specifically within the hip OA cohort, IL-6, MDC and IP10 were associated with pain and were also found to be present in synovial fluid and synovial membrane (except IL-6) of patients with hip OA. Conclusion OA may include different inflammatory subtypes according to affected joints and distinct inflammatory processes may drive OA in these joints. IL6, MDC and IP10 are associated with hip OA pain and these proteins may be able to provide additional information regarding pain in hip OA patients.