Attenuation of cartilage pathogenesis in post-traumatic osteoarthritis (PTOA) in mice by blocking the stromal derived factor 1 receptor (CXCR4) with the specific inhibitor, AMD3100.

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Nathan P ThomasLei Wei

Abstract

SDF-1 was found to infiltrate cartilage, decrease proteoglycan content, and increase MMP-13 activity after joint trauma. In this study, we tested the hypothesis that interference of the SDF-1/CXCR4 signaling pathway via AMD3100 can attenuate pathogenesis in a mouse model of PTOA. We also tested the predictive and confirmatory power of fluorescence molecular tomography (FMT) for cartilage assessment. AMD3100 was continuously delivered via mini-osmotic pumps. The extent of cartilage damage after AMD3100 or PBS treatment was assessed by histological analysis 2 months after PTOA was induced by surgical destabilization of the medial meniscus (DMM). Biochemical markers of PTOA were assessed via immunohistochemistry and in vivo fluorescence molecular tomography (FMT). Regression analysis was used to validate the predictive power of FMT measurements. Safranin-O staining revealed significant PTOA damage in the DMM/PBS mice, while the DMM/AMD3100 treated mice showed a significantly reduced response with minimal pathology. Immunohistochemistry showed that AMD3100 treatment markedly reduced typical PTOA marker expression in chondrocytes. FMT measurements showed decreased cathepsins and MMP activity in knee joints after treatment. The resul...Continue Reading

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Citations

Jun 27, 2015·Current Rheumatology Reports·Paxton M Moon, Frank Beier
Jun 21, 2016·International Journal of Molecular Sciences·Yonghui DongAnmin Chen
Nov 19, 2017·BMC Musculoskeletal Disorders·Dawei LiangLei Wei
Mar 8, 2017·Current Rheumatology Reports·Giovanni BernardiniAngela Santoni
Oct 7, 2015·Frontiers in Pharmacology·Alicia Arranz, Jorge Ripoll
Nov 7, 2019·Therapeutic Advances in Chronic Disease·Robert BraggSadanand Fulzele
Dec 23, 2016·Rheumatology·Thomas Hügle, Jeroen Geurts
Dec 19, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Lizette UtomoYvonne M Bastiaansen-Jenniskens

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