Ignite Creation Date:
2024-07-17 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06494813
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-10
First Post:
2024-07-02
Brief Title:
Biochemical Role of Matrix Metalloproteinase -9 in Rheumatoid Arthritis
Sponsor:
Sohag University
Organization:
Sohag University
Study Overview
Official Title:
Biochemical Role of Matrix Metalloproteinase -9 in Rheumatoid Arthritis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Rheumatoid arthritis RA is a systemic autoimmune pathology associated with a chronic inflammatory process which can damage both joints and extra-articular organs including the heart kidney lung digestive system eye skin and nervous systemCojocaru et al 2010 Conforti et al 2021
Rheumatoid arthritis affects most commonly the hand wrist and foot but it can also affect large joints IT is characterized by painful swollen joints that can severely impair physical function and quality of life and associated with increased mortality Sparks et al 2016 About 70 of patients with RA are women and peak incidence is between ages 50 and 60 years Sparks et al 2019
Matrix Metalloproteinases are a family of calcium-dependent endopeptidases with a zinc-binding active side More than 20 different MMPs are classified according to the particular substrates they degrade collagenases stromelysins gelatinases matrilysins membrane-type MMPs and others Moreover MMPs release growth factors from carrier proteins inactivate proteinase inhibitors and influence inflammatory cytokines and chemokines that can also be responsible for joint destructionNagase et al 2006
In the human body MMPs are synthesized in leukocytes macrophages endothelial cells and connective tissue cells such as chondrocytes and synoviocytes both found in the knee joint Matrix metalloproteinases are secreted as pre-proenzymes into the extracellular fluid where they can be activated by a variety of substances epidermal growth factor EGF vascular endothelial growth factor VEGF tumor necrosis factor-α TNF-α interleukin-1 IL-1 and other MMPs Conversely steroid hormones transforming growth factor-β TGF-β plasma proteins such as a2-macroglobulin and a1-antitrypsin and tissue inhibitors of metalloproteinases TIMPs can inhibit MMP activityVisse and Nagase 2003
The pathogenesis of RA is based on the fact that the patients body reacts to autoantigens eg citrullinated peptides or a foreign peptide eg a viral or bacterial peptide that is cross-reactive with an autoantigen Kwon and Ju 2021
Activated T cells B cells and monocytes infiltrate the synovial membrane in joints as that is where the autoantigens accumulate Cytokines and chemokines secreted by leukocytes such as tumor necrosis factor IL-6 and granulocyte colony-stimulating factors activate endothelial cells stimulate neovascularization and leukocyte migration and cause expansion of synovial fibroblast-like and macrophage-like cells Alivernini et al 2022 Expansion of these cells leads to a hyperplastic synovial lining layer referred to as a pannus The pannus invades the periarticular bone at the cartilage-bone junction and leads to the progressive destruction of cartilage and subchondral bone tissueAletaha and Smolen 2018
Matrix metalloproteinases are crucial for the pathogenesis of RA Synovial fibroblast-like cells having a tumor-like appearance secrete various proteases including MMPs that degrade ECM components mainly proteoglycans and collagens of articular cartilage in the affected joints Expression of the following MMPs is upregulated in synovial tissue MMP-1 -3 -9 and -13 Vincenti and Brinckerhoff 2002 Heard et al 2012 Araki and Mimura 2017
Rheumatoid arthritis affects most commonly the hand wrist and foot but it can also affect large joints IT is characterized by painful swollen joints that can severely impair physical function and quality of life and associated with increased mortality Sparks et al 2016 About 70 of patients with RA are women and peak incidence is between ages 50 and 60 years Sparks et al 2019
Matrix Metalloproteinases are a family of calcium-dependent endopeptidases with a zinc-binding active side More than 20 different MMPs are classified according to the particular substrates they degrade collagenases stromelysins gelatinases matrilysins membrane-type MMPs and others Moreover MMPs release growth factors from carrier proteins inactivate proteinase inhibitors and influence inflammatory cytokines and chemokines that can also be responsible for joint destructionNagase et al 2006
In the human body MMPs are synthesized in leukocytes macrophages endothelial cells and connective tissue cells such as chondrocytes and synoviocytes both found in the knee joint Matrix metalloproteinases are secreted as pre-proenzymes into the extracellular fluid where they can be activated by a variety of substances epidermal growth factor EGF vascular endothelial growth factor VEGF tumor necrosis factor-α TNF-α interleukin-1 IL-1 and other MMPs Conversely steroid hormones transforming growth factor-β TGF-β plasma proteins such as a2-macroglobulin and a1-antitrypsin and tissue inhibitors of metalloproteinases TIMPs can inhibit MMP activityVisse and Nagase 2003
The pathogenesis of RA is based on the fact that the patients body reacts to autoantigens eg citrullinated peptides or a foreign peptide eg a viral or bacterial peptide that is cross-reactive with an autoantigen Kwon and Ju 2021
Activated T cells B cells and monocytes infiltrate the synovial membrane in joints as that is where the autoantigens accumulate Cytokines and chemokines secreted by leukocytes such as tumor necrosis factor IL-6 and granulocyte colony-stimulating factors activate endothelial cells stimulate neovascularization and leukocyte migration and cause expansion of synovial fibroblast-like and macrophage-like cells Alivernini et al 2022 Expansion of these cells leads to a hyperplastic synovial lining layer referred to as a pannus The pannus invades the periarticular bone at the cartilage-bone junction and leads to the progressive destruction of cartilage and subchondral bone tissueAletaha and Smolen 2018
Matrix metalloproteinases are crucial for the pathogenesis of RA Synovial fibroblast-like cells having a tumor-like appearance secrete various proteases including MMPs that degrade ECM components mainly proteoglycans and collagens of articular cartilage in the affected joints Expression of the following MMPs is upregulated in synovial tissue MMP-1 -3 -9 and -13 Vincenti and Brinckerhoff 2002 Heard et al 2012 Araki and Mimura 2017
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None