scholarly journals Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis

2021 ◽  
Vol 22 (4) ◽  
pp. 1742
Author(s):  
Qichan Hu ◽  
Melanie Ecker
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Type Ii ◽  
Inhibitor Development ◽  
Matrix Metalloproteinase 13 ◽  
Promising Target

Osteoarthritis (OA) is a common degenerative disease characterized by the destruction of articular cartilage and chronic inflammation of surrounding tissues. Matrix metalloproteinase-13 (MMP-13) is the primary MMP involved in cartilage degradation through its particular ability to cleave type II collagen. Hence, it is an attractive target for the treatment of OA. However, the detailed molecular mechanisms of OA initiation and progression remain elusive, and, currently, there are no interventions available to restore degraded cartilage. This review fully illustrates the involvement of MMP-13 in the initiation and progression of OA through the regulation of MMP-13 activity at the molecular and epigenetic levels, as well as the strategies that have been employed against MMP-13. The aim of this review is to identify MMP-13 as an attractive target for inhibitor development in the treatment of OA.

scholarly journals Characterization of Selective Exosite-Binding Inhibitors of Matrix Metalloproteinase 13 That Prevent Articular Cartilage Degradation in Vitro

2014 ◽  
Vol 57 (22) ◽  
pp. 9598-9611 ◽  
Author(s):  
Timothy P. Spicer ◽  
Jianwen Jiang ◽  
Alexander B. Taylor ◽  
Jun Yong Choi ◽  
P. John Hart ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Cartilage Degradation ◽  
Matrix Metalloproteinase 13 ◽  
Binding Inhibitors

scholarly journals Interaction of HIF1α and β-catenin inhibits matrix metalloproteinase 13 expression and prevents cartilage damage in mice

2016 ◽  
Vol 113 (19) ◽  
pp. 5453-5458 ◽  
Author(s):  
Wafa Bouaziz ◽  
Johanna Sigaux ◽  
Dominique Modrowski ◽  
Claire-Sophie Devignes ◽  
Thomas Funck-Brentano ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Wnt Signaling ◽  
Cartilage Degradation ◽  
Conditional Knockout ◽  
Negative Regulator ◽  
Matrix Metalloproteinase 13 ◽  
The Impact ◽  
Mmp13 Expression

Low oxygen tension (hypoxia) regulates chondrocyte differentiation and metabolism. Hypoxia-inducible factor 1α (HIF1α) is a crucial hypoxic factor for chondrocyte growth and survival during development. The major metalloproteinase matrix metalloproteinase 13 (MMP13) is also associated with chondrocyte hypertrophy in adult articular cartilage, the lack of which protects from cartilage degradation and osteoarthritis (OA) in mice. MMP13 is up-regulated by the Wnt/β-catenin signaling, a pathway involved in chondrocyte catabolism and OA. We studied the role of HIF1α in regulating Wnt signaling in cartilage and OA. We used mice with conditional knockout of Hif1α (∆Hif1αchon) with joint instability. Specific loss of HIF1α exacerbated MMP13 expression and cartilage destruction. Analysis of Wnt signaling in hypoxic chondrocytes showed that HIF1α lowered transcription factor 4 (TCF4)–β-catenin transcriptional activity and inhibited MMP13 expression. Indeed, HIF1α interacting with β-catenin displaced TCF4 from MMP13 regulatory sequences. Finally, ΔHif1αchon mice with OA that were injected intraarticularly with PKF118-310, an inhibitor of TCF4–β-catenin interaction, showed less cartilage degradation and reduced MMP13 expression in cartilage. Therefore, HIF1α–β-catenin interaction is a negative regulator of Wnt signaling and MMP13 transcription, thus reducing catabolism in OA. Our study contributes to the understanding of the role of HIF1α in OA and highlights the HIF1α–β-catenin interaction, thus providing new insights into the impact of hypoxia in articular cartilage.

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