@article{gagliardi_loeser_schnabel_2024, title={A NOVEL MATRIKINE STIMULATED EQUINE SYNOVIAL FIBROBLAST AND CHONDROCYTE COCULTURE MODEL OF OSTEOARTHRITIS: A PROPOSED ALTERNATIVE TO TRADITIONAL LPS AND IL-1B MODELS}, volume={32}, ISSN={["1522-9653"]}, DOI={10.1016/j.joca.2024.03.044}, number={6}, journal={OSTEOARTHRITIS AND CARTILAGE}, author={Gagliardi, Rachel and Loeser, Richard F. and Schnabel, Lauren}, year={2024}, month={Jun}, pages={780–781} }
 @article{gagliardi_koch_loeser_schnabel_2024, title={Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype}, volume={43}, ISSN={0736-0266 1554-527X}, url={http://dx.doi.org/10.1002/jor.26004}, DOI={10.1002/jor.26004}, abstractNote={Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint. The objective of this study was to determine if matrikine stimulation of equine synovial fibroblasts and chondrocytes with fibronectin fragments (FN7-10) would result in an OA phenotype. We hypothesized that FN7-10 stimulation of equine articular cells would result in an OA phenotype with gene and protein expression changes similar to those previously described for human chondrocytes stimulated with FN7-10. Synovial fibroblasts and chondrocytes isolated from four horses were stimulated in monolayer culture for 6 or 18 h with 1 µM purified recombinant 42 kD FN7-10 in serum-free media. At the conclusion of stimulation, RNA was collected for targeted gene expression analysis and media for targeted protein production analysis. Consistent with our hypothesis, FN7-10 stimulation resulted in significant alterations to many important genes that are involved in OA pathogenesis including increased expression of IL-1β, IL-4, IL-6, CCL2/MCP-1, CCL5/RANTES, CXCL6/GCP-2, MMP-1, MMP-3, and MMP13. The results of this study suggest that the equine matrikine stimulation model of OA may prove useful for in vitro experiments leading up to preclinical trials.}, number={2}, journal={Journal of Orthopaedic Research}, publisher={Wiley}, author={Gagliardi, Rachel and Koch, Drew W. and Loeser, Richard and Schnabel, Lauren V.}, year={2024}, month={Nov}, pages={292–303} }
 @article{copp_flanders_gagliardi_gilbertie_sessions_chubinskaya_loeser_schnabel_diekman_2021, title={The combination of mitogenic stimulation and DNA damage induces chondrocyte senescence}, volume={29}, ISSN={["1522-9653"]}, url={https://doi.org/10.1016/j.joca.2020.11.004}, DOI={10.1016/j.joca.2020.11.004}, abstractNote={Cellular senescence is a phenotypic state characterized by stable cell-cycle arrest, enhanced lysosomal activity, and the secretion of inflammatory molecules and matrix degrading enzymes. Senescence has been implicated in osteoarthritis (OA) pathophysiology; however, the mechanisms that drive senescence induction in cartilage and other joint tissues are unknown. While numerous physiological signals are capable of initiating senescence, one emerging theme is that damaged cells convert to senescence in response to sustained mitogenic stimulation. The goal of this study was to develop an in vitro articular cartilage explant model to investigate the mechanisms of senescence induction.This study utilized healthy cartilage derived from cadaveric equine stifles and human ankles. Explants were irradiated to initiate DNA damage, and mitogenic stimulation was provided through serum-containing medium and treatment with transforming growth factor β1 and basic fibroblastic growth factor. Readouts of senescence were a quantitative flow cytometry assay to detect senescence-associated β galactosidase activity (SA-β-gal), immunofluorescence for p16 and γH2AX, and qPCR for the expression of inflammatory genes.Human cartilage explants required both irradiation and mitogenic stimulation to induce senescence as compared to baseline control conditions (7.16% vs 2.34% SA-β-gal high, p = 0.0007). These conditions also resulted in chondrocyte clusters within explants, a persistent DNA damage response, increased p16, and gene expression changes.Treatment of cartilage explants with mitogenic stimuli in the context of cellular damage reliably induces high levels of SA-β-gal activity and other senescence markers, which provides a physiologically relevant model system to investigate the mechanisms of senescence induction.}, number={3}, journal={OSTEOARTHRITIS AND CARTILAGE}, publisher={Elsevier BV}, author={Copp, M. E. and Flanders, M. C. and Gagliardi, R. and Gilbertie, J. M. and Sessions, G. A. and Chubinskaya, S. and Loeser, R. F. and Schnabel, L. and Diekman, B. O.}, year={2021}, month={Mar}, pages={402–412} }