Breaking down to rebuild: lymphatic ablation enhances osteoclast-driven regeneration
Matthijs Luxen, Francesca Lazzeri-Barcelo, Ralf H. Adams
Matthijs Luxen, Francesca Lazzeri-Barcelo, Ralf H. Adams
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Commentary

Breaking down to rebuild: lymphatic ablation enhances osteoclast-driven regeneration

Abstract

The fingertip is one of the only known complex structures in mammals that can fully regenerate following amputation. This phenomenon can be studied in mice using the amputation of the digit tip, the regenerative success of which has been shown to be reliant on effective bone clearance prior to new bone formation. In this issue of the JCI, Vishlaghi et al. investigated whether local lymphatic vessels are involved in this process. Interestingly, they found that inhibiting lymphangiogenesis resulted in accelerated clearance of damaged tissue and bone, thereby improving subsequent digit regeneration. This study is the first to our knowledge to report lymphatic involvement in digit regeneration and raises questions regarding the underlying mechanisms at play.

Authors

Matthijs Luxen, Francesca Lazzeri-Barcelo, Ralf H. Adams

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Figure 1

Lymphatic ablation promotes regeneration in a P3 digit amputation model.

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Lymphatic ablation promotes regeneration in a P3 digit amputation model....
(A) Overview of tissue structure within the digit tip. Amputation along the P2 axis leads to scarring and fibrosis without regeneration, whereas amputation along the more distal P3 axis leads to full regeneration. (B) Following P3 digit tip amputation, the damage site undergoes an osteoclast-driven bone resorption phase (7 days post-amputation [DPA]), followed by the formation of the regenerative blastema (10 DPA). At 28 DPA, the digit tip is fully regenerated. (C) Vishlaghi et al. (9) showed that inhibition of lymphatics during P3 digit amputation led to accumulation of both F4/80+ myeloid cells and RANKL-producing T cells at the damage site. RANKL promoted myeloid-to-osteoclast differentiation, thereby contributing to increased osteolytic activity. More efficient clearance of the amputated bone stump allowed for faster and improved bone regeneration.