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 inXenopus 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.

FGF‐stimulated tendon cells embrace a chondrogenic fate with BMP7 in newt tissue culture

“…In the present study, we found that tendon-derived cells that proliferated upon stimulation by FGFs can respond to BMP, differentiating into Sox9-positive chondrocytes; FGF might promote not only cell proliferation but also cellular competency to be able to differentiate into chondrocytes, suggesting that the combination of FGF and BMP is important for the transdifferentiation of chondrocytes from tendonderived cells. Our recent study using Xenopus as a model system suggested that FGF can induce matrix metalloproteinase expression in remaining articular cartilage and that BMP might be secreted from the remaining articular cartilage via ECM degradation (Matsubara et al, 2023). Combining these results, it is postulated that functional joints are regenerated through a scheme similar to that summarized in To validate these in vivo schemes, we are planning to conduct in vivo cell fate tracking using genetically modified Iberian ribbed newts (P. waltl).…”

“…Thus, FGF, BMP, and PDGF may function as regeneration inducers during joint regeneration in amphibians. Moreover, in X. laevis, the remaining stump tissues may be activated by signals derived from the blastema to achieve proper tissue connection for functional joint regeneration (Matsubara et al, 2023).…”