Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes
Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db<sup>−</sup>/db<sup>−</sup>) revealed accelerated activation of pa...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/12/2/134 |
| _version_ | 1797478702451261440 |
|---|---|
| author | Johannes Maximilian Wagner Felix Reinkemeier Christoph Wallner Mehran Dadras Stephanie Dittfeld Marius Drysch Alexander Sogorski Maxi von Glinski Marcus Lehnhardt Björn Behr Mustafa Becerikli |
| author_facet | Johannes Maximilian Wagner Felix Reinkemeier Christoph Wallner Mehran Dadras Stephanie Dittfeld Marius Drysch Alexander Sogorski Maxi von Glinski Marcus Lehnhardt Björn Behr Mustafa Becerikli |
| author_sort | Johannes Maximilian Wagner |
| collection | DOAJ |
| description | Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db<sup>−</sup>/db<sup>−</sup>) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. <i>Mmp3</i>, <i>Mmp9</i>, <i>Mmp13</i> and gene expression of MMP inhibitor <i>Timp2</i> was significantly higher in regenerating bone fractures of db<sup>−</sup>/db<sup>−</sup> compared to wild type animals. <i>Timp1</i> and metalloproteinase <i>AdamTS4</i> showed no differences. In the second part, we locally applied a single dose (1 µL of 5 µM solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db<sup>−</sup>/db<sup>−</sup>. We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db<sup>−</sup>/db<sup>−</sup> were restored significantly by application of Marimastat compared to PBS controls (<i>n</i> = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes. |
| first_indexed | 2024-03-09T21:35:22Z |
| format | Article |
| id | doaj.art-6a07295f57ec4ae4839a67cf51eb1d32 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T21:35:22Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-6a07295f57ec4ae4839a67cf51eb1d322023-11-23T20:44:36ZengMDPI AGLife2075-17292022-01-0112213410.3390/life12020134Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in DiabetesJohannes Maximilian Wagner0Felix Reinkemeier1Christoph Wallner2Mehran Dadras3Stephanie Dittfeld4Marius Drysch5Alexander Sogorski6Maxi von Glinski7Marcus Lehnhardt8Björn Behr9Mustafa Becerikli10Department of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyDepartment of Plastic and Reconstructive Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, GermanyPatients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db<sup>−</sup>/db<sup>−</sup>) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. <i>Mmp3</i>, <i>Mmp9</i>, <i>Mmp13</i> and gene expression of MMP inhibitor <i>Timp2</i> was significantly higher in regenerating bone fractures of db<sup>−</sup>/db<sup>−</sup> compared to wild type animals. <i>Timp1</i> and metalloproteinase <i>AdamTS4</i> showed no differences. In the second part, we locally applied a single dose (1 µL of 5 µM solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db<sup>−</sup>/db<sup>−</sup>. We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db<sup>−</sup>/db<sup>−</sup> were restored significantly by application of Marimastat compared to PBS controls (<i>n</i> = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes.https://www.mdpi.com/2075-1729/12/2/134bone regenerationdiabetesgene expressionMMPMarimastat |
| spellingShingle | Johannes Maximilian Wagner Felix Reinkemeier Christoph Wallner Mehran Dadras Stephanie Dittfeld Marius Drysch Alexander Sogorski Maxi von Glinski Marcus Lehnhardt Björn Behr Mustafa Becerikli Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes Life bone regeneration diabetes gene expression MMP Marimastat |
| title | Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes |
| title_full | Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes |
| title_fullStr | Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes |
| title_full_unstemmed | Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes |
| title_short | Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes |
| title_sort | inhibition of pathological increased matrix metalloproteinase mmp activity for improvement of bone regeneration in diabetes |
| topic | bone regeneration diabetes gene expression MMP Marimastat |
| url | https://www.mdpi.com/2075-1729/12/2/134 |
| work_keys_str_mv | AT johannesmaximilianwagner inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT felixreinkemeier inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT christophwallner inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT mehrandadras inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT stephaniedittfeld inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT mariusdrysch inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT alexandersogorski inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT maxivonglinski inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT marcuslehnhardt inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT bjornbehr inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes AT mustafabecerikli inhibitionofpathologicalincreasedmatrixmetalloproteinasemmpactivityforimprovementofboneregenerationindiabetes |