Cytochalasin D Stimulates MAP Kinase Phosphorylation and MMP-13 Release in Normal Human Chondrocytes

Undergraduates: Manisha Mishra, John A. Collins, PhD.

Faculty Advisor: Richard Loeser
Department: Biology

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Osteoarthritis (OA) is the most common form of arthritis and one of the leading causes of pain and disability in older adults. Human chondrocytes that have high expression of Matrix Metallopeptidase 13 (MMP-13) experience matrix destruction, which results in cell deterioration and death. MMP-13 is key in OA since it is the enzyme that is primarily responsible for the degradation of type II collagen, a key structural protein in the joint. MMP-13 activity is regulated by mitogen-activated (MAP) kinase proteins, which also control multiple cell signaling pathways. The purpose of this study was to identify the role of the cytoskeleton in the release of MMP-13 in human chondrocytes using the reagent Cytochalasin D, a mycotoxin that restructures the cytoskeleton by the inhibiting actin polymerization. Levels of MMP-13 and reactive oxygen species release were measured and phosphorylation of MAP kinases was observed. ¿¿It was seen that Cytochalasin D increases production of MMP-13. The findings of this study suggest that (1) correlation between inhibition of actin polymerization and release of MMP-13 and (2) the disruption of cytoskeletons results in the activation of catabolic cell signaling pathways in human chondrocytes. While other studies have demonstrated the effect of Cytochalasin D on the physical restructuring of the cytoskeletal networks, this study was the first to analyze the effects of the cytoskeleton rearrangement on MMP-13 levels in chondrocytes.