ECM degradation in the stump region induced by Fgf during functional joint regeneration in frogs

Abstract

Previous studies indicated the importance of the reciprocal interactions between residual tissues in the stump and the newly formed blastema for achieving functional joint regeneration after amputation at the joint level in newts. This reciprocal interaction during regeneration was named "reintegration". When this reintegration mechanism was evoked in Xenopus leavis, regeneration of a functional joint was induced in frogs. Interestingly, degradation of extracellular matrix (ECM) in the remaining joint cartilage was observed during regeneration in both newts and frogs. Histological and gene expression analyses suggested that the degradation of Type II collagen in the cartilage of the articular head might be performed by matrix metalloproteases (Mmps) which were transiently expressed after amputation. We found that fibroblast growth factor (Fgf) induced Mmps expression in the cartilage of the articular head. These results support the possibility that the Fgf signal induces ECM degradation in joint tissues via Mmps expression and that the ECM degradation and subsequent bone morphogenetic protein (Bmp) secretion promote cell proliferation, migration, and differentiation of the cells in the blastema to achieve functional joint regeneration.