The paper has been published in the Developmental Biology.

The research, which was initiated at Gakushuin University and led by Dr. Haruka Matsubara (currently at the Department of Life Sciences, Faculty of Medicine, Tottori University), has been published in the Developmental Biology. The paper is titled "Reintegration of blastema and stump by reciprocal interaction for functional joint regeneration in frogs."

In this study, we elucidated a mechanism of “reintegration” in joint regeneration, in which reciprocal interactions between the stump tissue remaining after amputation and the newly formed blastema are essential for restoring functional joints. Notably, we demonstrated that induction of this reintegration process in African clawed frogs (Xenopus laevis) enabled functional regeneration of the elbow joint. During this regenerative process, the extracellular matrix (ECM) of the articular cartilage undergoes degradation, mediated by matrix metalloproteinase 1 (Mmp1), whose expression is induced by fibroblast growth factor (Fgf). Our findings further suggest that ECM degradation by Mmp1 facilitates cell proliferation and differentiation, ultimately contributing to the reconstruction of a functional joint.

Reintegration of blastema and stump by reciprocal interaction for functional joint regeneration in frogs Matsubara, H., Inoue, T. and Agata, K. Dev Biol , 525: 282-293, 2025 https://doi.org/10.1016/j.ydbio.2025.06.011

During joint regeneration, active cellular contributions from the stump region—comprising multiple tissue types—are observed. The regenerative signal fibroblast growth factor (Fgf) induces the expression of matrix metalloproteinases (Mmps) in this region, promoting tissue degradation. This degradation, in turn, enhances bone morphogenetic protein (Bmp) signaling, as indicated by increased pSmad activity, at the interface between the blastema and the stump region. These reciprocal interactions together drive the characteristic reintegration response required for successful joint regeneration.

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