Vegfc-expressing cells form heterotopic bone after musculoskeletal injury

Neda Vishlaghi, Lei Guo, Danielle Griswold-Wheeler, Yuxiao Sun, Cori Booker, Janna L. Crossley, Alec C. Bancroft, Conan Juan, Sneha Korlakunta, Sowmya Ramesh, Chase A. Pagani, Lin Xu, Aaron W. James, Robert J. Tower, Michael Dellinger*, Benjamin Levi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. While the effect of HO on blood vessels is well established, little is known about its impact on lymphatic vessels. Here, we use a mouse model of traumatic HO to investigate the relationship between HO and lymphatic vessels. We show that injury triggers lymphangiogenesis at the injury site, which is associated with elevated vascular endothelial growth factor C (VEGF-C) levels. Through single-cell transcriptomic analyses, we identify mesenchymal progenitor cells and tenocytes as sources of Vegfc. We demonstrate by lineage tracing that Vegfc-expressing cells undergo osteochondral differentiation and contribute to the formation of HO. Last, we show that Vegfc haploinsufficiency results in a nearly 50% reduction in lymphangiogenesis and HO formation. These findings shed light on the complex mechanisms underlying HO formation and its impact on lymphatic vessels.

Original languageEnglish
Article number114049
JournalCell Reports
Issue number4
StatePublished - 23 Apr 2024
Externally publishedYes


  • CP: Cell biology
  • CP: Developmental biology
  • MPCs
  • Vegfc, VEGFC
  • heterotopic ossification
  • lymphangiogenesis


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