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  1. Article ; Online: Systems-based identification of the Hippo pathway for promoting fibrotic mesenchymal differentiation in systemic sclerosis.

    Ma, Feiyang / Tsou, Pei-Suen / Gharaee-Kermani, Mehrnaz / Plazyo, Olesya / Xing, Xianying / Kirma, Joseph / Wasikowski, Rachael / Hile, Grace A / Harms, Paul W / Jiang, Yanyun / Xing, Enze / Nakamura, Mio / Ochocki, Danielle / Brodie, William D / Pillai, Shiv / Maverakis, Emanual / Pellegrini, Matteo / Modlin, Robert L / Varga, John /
    Tsoi, Lam C / Lafyatis, Robert / Kahlenberg, J Michelle / Billi, Allison C / Khanna, Dinesh / Gudjonsson, Johann E

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 210

    Abstract: Systemic sclerosis (SSc) is a devastating autoimmune disease characterized by excessive production and accumulation of extracellular matrix, leading to fibrosis of skin and other internal organs. However, the main cellular participants in SSc skin ... ...

    Abstract Systemic sclerosis (SSc) is a devastating autoimmune disease characterized by excessive production and accumulation of extracellular matrix, leading to fibrosis of skin and other internal organs. However, the main cellular participants in SSc skin fibrosis remain incompletely understood. Here using differentiation trajectories at a single cell level, we demonstrate a dual source of extracellular matrix deposition in SSc skin from both myofibroblasts and endothelial-to-mesenchymal-transitioning cells (EndoMT). We further define a central role of Hippo pathway effectors in differentiation and homeostasis of myofibroblast and EndoMT, respectively, and show that myofibroblasts and EndoMTs function as central communication hubs that drive key pro-fibrotic signaling pathways in SSc. Together, our data help characterize myofibroblast differentiation and EndoMT phenotypes in SSc skin, and hint that modulation of the Hippo pathway may contribute in reversing the pro-fibrotic phenotypes in myofibroblasts and EndoMTs.
    MeSH term(s) Humans ; Hippo Signaling Pathway ; Fibrosis ; Scleroderma, Systemic/pathology ; Myofibroblasts/metabolism ; Endothelial Cells/metabolism ; Skin/pathology ; Fibroblasts/metabolism
    Language English
    Publishing date 2024-01-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44645-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Endurance running during late murine adolescence results in a stronger anterior cruciate ligament and flatter posterior tibial slopes compared to controls.

    Ochocki, Danielle N / Loflin, Benjamin E / Ahn, Taeyong / Colglazier, Kaitlyn A / Young, Andrew R / Snider, Anna A / Bueckers, Elizabeth P / Wojtys, Edward M / Schlecht, Stephen H

    Journal of experimental orthopaedics

    2022  Volume 9, Issue 1, Page(s) 3

    Abstract: Background: Anterior cruciate ligament (ACL) injury rates continue to rise among youth involved in recreational and competitive athletics, requiring a better understanding of how the knee structurally and mechanically responds to activity during ... ...

    Abstract Background: Anterior cruciate ligament (ACL) injury rates continue to rise among youth involved in recreational and competitive athletics, requiring a better understanding of how the knee structurally and mechanically responds to activity during musculoskeletal growth. Little is understood about how anatomical risk factors for ACL injury (e.g., small ACL size, narrow intercondylar notch, and steep posterior tibial slope) develop and respond to increased physical activity throughout growth. We hypothesized that the ACL-complex of mice engaged in moderate to strenuous physical activity (i.e., endurance running) throughout late adolescence and young adulthood would positively functionally adapt to repetitive load perturbations.
    Methods: Female C57BL6/J mice (8 weeks of age) were either provided free access to a standard cage wheel with added resistance (n = 18) or normal cage activity (n = 18), for a duration of 4 weeks. Daily distance ran, weekly body and food weights, and pre- and post-study body composition measures were recorded. At study completion, muscle weights, three-dimensional knee morphology, ACL cross-sectional area, and ACL mechanical properties of runners and nonrunners were quantified. Statistical comparisons between runners and nonrunners were assessed using a two-way analysis of variance and a Tukey multiple comparisons test, with body weight included as a covariate.
    Results: Runners had larger quadriceps (p = 0.02) and gastrocnemius (p = 0.05) muscles, but smaller hamstring (p = 0.05) muscles, compared to nonrunners. Though there was no significant difference in ACL size (p = 0.24), it was 13% stronger in runners (p = 0.03). Additionally, both the posterior medial and lateral tibial slopes were 1.2 to 2.2 degrees flatter than those of nonrunners (p < 0.01).
    Conclusions: Positive functional adaptations of the knee joint to moderate to strenuous exercise in inbred mice offers hope that that some anatomical risk factors for ACL injury may be reduced through habitual physical activity. However, confirmation that a similar response to loading occurs in humans is needed.
    Language English
    Publishing date 2022-01-03
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2780021-0
    ISSN 2197-1153
    ISSN 2197-1153
    DOI 10.1186/s40634-021-00439-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Morphology of Mouse Anterior Cruciate Ligament-Complex Changes Following Exercise During Pubertal Growth.

    Schlecht, Stephen H / Martin, Colin T / Ochocki, Danielle N / Nolan, Bonnie T / Wojtys, Edward M / Ashton-Miller, James A

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society

    2019  Volume 37, Issue 9, Page(s) 1910–1919

    Abstract: Postnatal development and the physiological loading response of the anterior cruciate ligament (ACL) complex (ACL proper, entheses, and bony morphology) is not well understood. We tested whether the ACL-complex of two inbred mouse strains that ... ...

    Abstract Postnatal development and the physiological loading response of the anterior cruciate ligament (ACL) complex (ACL proper, entheses, and bony morphology) is not well understood. We tested whether the ACL-complex of two inbred mouse strains that collectively encompass the musculoskeletal variation observed in humans would demonstrate significant morphological differences following voluntary cage-wheel running during puberty compared with normal cage activity controls. Female A/J and C57BL/6J (B6) 6-week-old mice were provided unrestricted access to a standard cage-wheel for 4 weeks. A/J-exercise mice showed a 6.3% narrower ACL (p = 0.64), and a 20.1% more stenotic femoral notch (p < 0.01) while B6-exercise mice showed a 12.3% wider ACL (p = 0.10), compared with their respective controls. Additionally, A/J-exercise mice showed a 5.3% less steep posterior medial tibial slope (p = 0.07) and an 8.8% less steep posterior lateral tibial slope (p = 0.07), while B6-exercise mice showed a 9.8% more steep posterior medial tibial slope (p < 0.01) than their respective controls. A/J-exercise mice also showed more reinforcement of the ACL tibial enthesis with a 20.4% larger area (p < 0.01) of calcified fibrocartilage distributed at a 29.2% greater depth (p = 0.02) within the tibial enthesis, compared with their controls. These outcomes suggest exercise during puberty significantly influences ACL-complex morphology and that inherent morphological differences between these mice, as observed in their less active genetically similar control groups, resulted in a divergent phenotypic outcome between mouse strains. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1910-1919, 2019.
    MeSH term(s) Animals ; Anterior Cruciate Ligament/pathology ; Anterior Cruciate Ligament Injuries/etiology ; Female ; Femur/pathology ; Knee Joint/pathology ; Mice ; Mice, Inbred C57BL ; Physical Conditioning, Animal ; Puberty/physiology ; Tibia/pathology
    Language English
    Publishing date 2019-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 605542-4
    ISSN 1554-527X ; 0736-0266
    ISSN (online) 1554-527X
    ISSN 0736-0266
    DOI 10.1002/jor.24328
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1879: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: State of the mineralized tissue comprising the femoral ACL enthesis in young women with an ACL failure.

    Patton, Daniella M / Ochocki, Danielle N / Martin, Colin T / Casden, Michael / Jepsen, Karl J / Ashton-Miller, James A / Wojtys, Edward M / Schlecht, Stephen H

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society

    2021  Volume 40, Issue 4, Page(s) 826–837

    Abstract: Despite poor graft integration among some patients that undergo an anterior cruciate ligament (ACL) reconstruction, there has been little consideration of the bone quality into which the ACL femoral tunnel is drilled and the graft is placed. Bone mineral ...

    Abstract Despite poor graft integration among some patients that undergo an anterior cruciate ligament (ACL) reconstruction, there has been little consideration of the bone quality into which the ACL femoral tunnel is drilled and the graft is placed. Bone mineral density of the knee decreases following ACL injury. However, trabecular and cortical architecture differences between injured and non-injured femoral ACL entheses have not been reported. We hypothesize that injured femoral ACL entheses will show significantly less cortical and trabecular mass compared with non-injured controls. Femoral ACL enthesis explants from 54 female patients (13-25 years) were collected during ACL reconstructive surgery. Control explants (n = 12) were collected from seven donors (18-36 years). Injured (I) femoral explants differed from those of non-injured (NI) controls with significantly less (p ≤ 0.001) cortical volumetric bone mineral density (vBMD) (NI: 736.1-867.6 mg/cm
    MeSH term(s) Anterior Cruciate Ligament/surgery ; Anterior Cruciate Ligament Injuries/surgery ; Anterior Cruciate Ligament Reconstruction ; Female ; Femur/surgery ; Humans ; Knee Joint/surgery ; Male
    Language English
    Publishing date 2021-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 605542-4
    ISSN 1554-527X ; 0736-0266
    ISSN (online) 1554-527X
    ISSN 0736-0266
    DOI 10.1002/jor.25130
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1879: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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