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  1. Article ; Online: The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors

    Nabangshu Das / Colette Benko / Sean E. Gill / Antoine Dufour

    Pharmaceuticals, Vol 14, Iss 31, p

    2021  Volume 31

    Abstract: Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat ® , have failed in Phase III clinical trials. As an alternative ... ...

    Abstract Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat ® , have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches, such as proteomics and N-terminomics, to identify new MMP substrates. We present some examples of new MMP substrates and their implications in regulating biological functions. By characterizing the roles and substrates of individual MMP, MMP inhibitors could be utilized more effectively in the optimal disease context or in diseases never tested before where MMP activity is elevated and contributing to disease progression.
    Keywords matrix metalloproteinases (MMPs) ; protease ; tissue inhibitors of metalloproteinases (TIMPs) ; exosite ; small molecule inhibitors ; monoclonal antibodies ; proteomics ; N-terminomics ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 540
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

    Roman J. Krawetz / Leila Larijani / Jessica May Corpuz / Nicoletta Ninkovic / Nabangshu Das / Alexandra Olsen / Nicholas Mohtadi / Alexander Rezansoff / Antoine Dufour

    Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-

    2023  Volume 18

    Abstract: Abstract Background Osteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no ... ...

    Abstract Abstract Background Osteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no current treatments which can reverse the joint damage occurring during the pathogenesis of the disease. While many groups are investigating the use of stem cell therapies in the treatment of OA, we still don’t have a clear understanding of the role of these cells in the body, including heterogeneity of tissue resident adult mesenchymal progenitor cells (MPCs). Methods In the current study, we examined MPCs from the synovium and individuals with or without a traumatic knee joint injury and explored the chondrogenic differentiation capacity of these MPCs in vitro and in vivo. Results We found that there is heterogeneity of MPCs with the adult synovium and distinct sub-populations of MPCs and the abundancy of these sub-populations change with joint injury. Furthermore, only some of these sub-populations have the ability to effect cartilage repair in vivo. Using an unbiased proteomics approach, we were able to identify cell surface markers that identify this pro-chondrogenic MPC population in normal and injured joints, specifically CD82LowCD59+ synovial MPCs have robust cartilage regenerative properties in vivo. Conclusions The results of this study clearly show that cells within the adult human joint can impact cartilage repair and that these sub-populations exist within joints that have undergone a traumatic joint injury. Therefore, these populations can be exploited for the treatment of cartilage injuries and OA in future clinical trials.
    Keywords Mesenchymal progenitor cells ; Osteoarthritis ; Inflammation ; ACL injury ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
    Subject code 616
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Matrix Metalloproteases as Influencers of the Cells’ Social Media

    Daniel Young / Nabangshu Das / Anthonia Anowai / Antoine Dufour

    International Journal of Molecular Sciences, Vol 20, Iss 16, p

    2019  Volume 3847

    Abstract: Matrix metalloproteinases (MMPs) have been studied in the context of cancer due to their ability to increase cell invasion, and were initially thought to facilitate metastasis solely through the degradation of the extracellular matrix (ECM). MMPs have ... ...

    Abstract Matrix metalloproteinases (MMPs) have been studied in the context of cancer due to their ability to increase cell invasion, and were initially thought to facilitate metastasis solely through the degradation of the extracellular matrix (ECM). MMPs have also been investigated in the context of their ECM remodeling activity in several acute and chronic inflammatory diseases. However, after several MMP inhibitors failed in phase III clinical trials, a global reassessment of their biological functions was undertaken, which has revealed multiple unanticipated functions including the processing of chemokines, cytokines, and cell surface receptors. Despite what their name suggests, the matrix aspect of MMPs could contribute to a lesser part of their physiological functions in inflammatory diseases, as originally anticipated. Here, we present examples of MMP substrates implicated in cell signaling, independent of their ECM functions, and discuss the impact for the use of MMP inhibitors.
    Keywords matrix metalloproteinases (MMPs) ; protease ; inflammation ; signaling ; invasion ; apoptosis ; chemokine ; cytokine ; proteomics ; interferon ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis

    Nabangshu Das / Luiz G. N. de Almeida / Afshin Derakhshani / Daniel Young / Kobra Mehdinejadiani / Paul Salo / Alexander Rezansoff / Gregory D. Jay / Christian P. Sommerhoff / Tannin A. Schmidt / Roman Krawetz / Antoine Dufour

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 20

    Abstract: Altered expression and function of the extracellular matrix protein PRG4 have been associated with osteoarthritis. Here, the authors show that mast cell tryptase β cleaves PRG4, resulting in a reduction of lubrication and activation of inflammation in ... ...

    Abstract Altered expression and function of the extracellular matrix protein PRG4 have been associated with osteoarthritis. Here, the authors show that mast cell tryptase β cleaves PRG4, resulting in a reduction of lubrication and activation of inflammation in this context.
    Keywords Science ; Q
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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