The release of an ERK-activating factor from cartilage explants in response to trauma

Mechanical injury to cartilage predisposes to premature degenerative arthritis but little is understood of the chondrocytic response to injury at the cellular and molecutar level. We have shown that the extracellular regulated kinase (ERK), the original mitogen activated protein (MAP) kinase, is strongly activated in porcine articular cartilage upon scarification in vivo, or following cutting of rested cartilage explants in vitro. Activation occurs within minutes and is sustained for 24-48 h. It appears to be mediated by a soluble factor which is released into the culture medium by damaged cartilage. The factor is thermolabile and retained by dialysis membrane (10 kDa cut-off). We have purified the factor through a series of chromatography steps (anion and cation exvhange, gel filtration and agarose-heparin columns), and are awaiting identification. It represents a potential homeostatic mechanism in response to injury, and could play a role in normal metabolism and degenerative arthritis.