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  1. Article ; Online: Standardized Histomorphometric Evaluation of Osteoarthritis in a Surgical Mouse Model.

    Pinamont, William J / Yoshioka, Natalie K / Young, Gregory M / Karuppagounder, Vengadeshprabhu / Carlson, Elijah L / Ahmad, Adeel / Elbarbary, Reyad / Kamal, Fadia

    Journal of visualized experiments : JoVE

    2020  , Issue 159

    Abstract: One of the most prevalent joint disorders in the United States, osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, primarily in the hip and knee joints, which results in significant impacts on patient mobility and ... ...

    Abstract One of the most prevalent joint disorders in the United States, osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, primarily in the hip and knee joints, which results in significant impacts on patient mobility and quality of life. To date, there are no existing curative therapies for OA able to slow down or inhibit cartilage degeneration. Presently, there is an extensive body of ongoing research to understand OA pathology and discover novel therapeutic approaches or agents that can efficiently slow down, stop, or even reverse OA. Thus, it is crucial to have a quantitative and reproducible approach to accurately evaluate OA-associated pathological changes in the joint cartilage, synovium, and subchondral bone. Currently, OA severity and progression are primarily assessed using the Osteoarthritis Research Society International (OARSI) or Mankin scoring systems. In spite of the importance of these scoring systems, they are semiquantitative and can be influenced by user subjectivity. More importantly, they fail to accurately evaluate subtle, yet important, changes in the cartilage during the early disease states or early treatment phases. The protocol we describe here uses a computerized and semiautomated histomorphometric software system to establish a standardized, rigorous, and reproducible quantitative methodology for the evaluation of joint changes in OA. This protocol presents a powerful addition to the existing systems and allows for more efficient detection of pathological changes in the joint.
    MeSH term(s) Animals ; Bone Marrow/pathology ; Calibration ; Cartilage, Articular/pathology ; Cell Count ; Chondrocytes/pathology ; Disease Models, Animal ; Knee Joint/pathology ; Male ; Mice, Inbred C57BL ; Osteoarthritis/pathology ; Osteoarthritis/surgery ; Phenotype ; Quality of Life ; Reference Standards ; Software ; Staining and Labeling ; Synovial Membrane/pathology ; Tibia/pathology
    Language English
    Publishing date 2020-05-06
    Publishing country United States
    Document type Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/60991
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Standardized histomorphometric evaluation of osteoarthritis in a surgical mouse model

    Pinamont, William J / Yoshioka, Natalie K / Young, Gregory M / Karuppagounder, Vengadeshprabhu / Carlson, Elijah L / Ahmad, Adeel / Elbarbary, Reyad / Kamal, Fadia

    Journal of visualized experiments. 2020 May 06, , no. 159

    2020  

    Abstract: One of the most prevalent joint disorders in the United States, osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, primarily in the hip and knee joints, which results in significant impacts on patient mobility and ... ...

    Abstract One of the most prevalent joint disorders in the United States, osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, primarily in the hip and knee joints, which results in significant impacts on patient mobility and quality of life. To date, there are no existing curative therapies for OA able to slow down or inhibit cartilage degeneration. Presently, there is an extensive body of ongoing research to understand OA pathology and discover novel therapeutic approaches or agents that can efficiently slow down, stop, or even reverse OA. Thus, it is crucial to have a quantitative and reproducible approach to accurately evaluate OA-associated pathological changes in the joint cartilage, synovium, and subchondral bone. Currently, OA severity and progression are primarily assessed using the Osteoarthritis Research Society International (OARSI) or Mankin scoring systems. In spite of the importance of these scoring systems, they are semiquantitative and can be influenced by user subjectivity. More importantly, they fail to accurately evaluate subtle, yet important, changes in the cartilage during the early disease states or early treatment phases. The protocol we describe here uses a computerized and semiautomated histomorphometric software system to establish a standardized, rigorous, and reproducible quantitative methodology for the evaluation of joint changes in OA. This protocol presents a powerful addition to the existing systems and allows for more efficient detection of pathological changes in the joint.
    Keywords animal models ; cartilage ; computer software ; hips ; knees ; mice ; osteoarthritis ; patients ; quality of life ; therapeutics
    Language English
    Dates of publication 2020-0506
    Size p. e60991.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/60991
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis.

    Carlson, Elijah L / Karuppagounder, Vengadeshprabhu / Pinamont, William J / Yoshioka, Natalie K / Ahmad, Adeel / Schott, Eric M / Le Bleu, Heather K / Zuscik, Michael J / Elbarbary, Reyad A / Kamal, Fadia

    Science translational medicine

    2021  Volume 13, Issue 580

    Abstract: Osteoarthritis (OA) is a debilitating joint disease characterized by progressive cartilage degeneration, with no available disease-modifying therapy. OA is driven by pathological chondrocyte hypertrophy (CH), the cellular regulators of which are unknown. ...

    Abstract Osteoarthritis (OA) is a debilitating joint disease characterized by progressive cartilage degeneration, with no available disease-modifying therapy. OA is driven by pathological chondrocyte hypertrophy (CH), the cellular regulators of which are unknown. We have recently reported the therapeutic efficacy of G protein-coupled receptor kinase 2 (GRK2) inhibition in other diseases by recovering protective G protein-coupled receptor (GPCR) signaling. However, the role of GPCR-GRK2 pathway in OA is unknown. Thus, in a surgical OA mouse model, we performed genetic GRK2 deletion in chondrocytes or pharmacological inhibition with the repurposed U.S. Food and Drug Administration (FDA)-approved antidepressant paroxetine. Both GRK2 deletion and inhibition prevented CH, abated OA progression, and promoted cartilage regeneration. Supporting experiments with cultured human OA cartilage confirmed the ability of paroxetine to mitigate CH and cartilage degradation. Our findings present elevated GRK2 signaling in chondrocytes as a driver of CH in OA and identify paroxetine as a disease-modifying drug for OA treatment.
    MeSH term(s) Animals ; Cartilage ; Cartilage, Articular ; Chondrocytes ; G-Protein-Coupled Receptor Kinase 2 ; Mice ; Osteoarthritis/drug therapy ; Paroxetine/pharmacology ; Paroxetine/therapeutic use
    Chemical Substances Paroxetine (41VRH5220H) ; G-Protein-Coupled Receptor Kinase 2 (EC 2.7.11.16)
    Language English
    Publishing date 2021-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.aau8491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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