Digit regeneration in mice is stimulated by sequential treatment with FGF2 and BMP2
Epimorphic regeneration in mice is stimulated at a non-regenerative digit amputation by sequential treatment with FGF2 and BMP2 (FGF2→BMP2). FGF2 stimulates digit amputation wound cells to form a blastema and BMP2 induces blastema differentiation to regenerate the amputated distal phalangeal element, albeit imperfectly. The formation of a phalangeal growth plate suggests that the induced regenerate recapitulates embryonic development and cell lineage studies show that wound cells that enter the blastema cells are positionally re-specified during regeneration. FGF2→BMP2 treatment also stimulates a blastema-independent response that regenerates a synovial joint complex containing stump-derived tendon, ligament and a sesamoid-like bone. Together the blastema-dependent and blastema-independent responses can result in the regeneration of all skeletal structures removed by amputation. The induced regeneration response demonstrates the availability of regeneration competent cells at a non-regenerating wound, and that FGF and BMP signaling is sufficient to trigger a regenerative outcome at wounds that heal by fibrosis.
Authors
- Ken Muneoka (ORCID: https://orcid.org/0000-0002-7520-6869)
- Connor P. Dolan (ORCID: https://orcid.org/0000-0001-7002-9341)
- Katherine Zimmel (ORCID: https://orcid.org/0000-0002-8243-6953)
- Osama Qureshi (ORCID: https://orcid.org/0000-0002-2495-7726)
- Yu‐Lieh Lin (ORCID: https://orcid.org/0000-0001-6487-4282)
- Manjong Han (ORCID: https://orcid.org/0009-0000-3223-5101)
- Larry J. Suva (ORCID: https://orcid.org/0000-0002-2892-9757)
- Regina Brunauer (ORCID: https://orcid.org/0000-0001-9384-5501)
- Lindsay Dawson (ORCID: https://orcid.org/0000-0002-4903-6050)
- James J. Cai (ORCID: https://orcid.org/0000-0002-8081-6725)
- Mingquan Yan (ORCID: https://orcid.org/0000-0003-3826-0492)
- Benjamin B. Bartelle (ORCID: https://orcid.org/0000-0002-5044-369X)
- Ling Yu (ORCID: https://orcid.org/0000-0002-8781-3033)
- Daniel Osorio Hurtado
- C. Addison Smith
Institutions
- Tulane University (US)
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA (AT)
- Ludwig Boltzmann Institute for Digital Health and Prevention (AT)
- Arizona State University (US)
- Texas A&M University (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1038/s41467-026-72066-8
- Primary Topic
- Tendon Structure and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Tulane University
- Defense Advanced Research Projects Agency
- National Institute on Aging
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- U.S. Army Research Institute of Environmental Medicine