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<p>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.</p>

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Digit regeneration in mice is stimulated by sequential treatment with FGF2 and BMP2

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Ling Yu,
  • Mingquan Yan,
  • Katherine Zimmel Scaturro,
  • Osama Qureshi,
  • Yu-Lieh Lin,
  • Benjamin B. Bartelle,
  • C. Addison Smith,
  • Daniel Osorio Hurtado,
  • James J. Cai,
  • Lindsay A. Dawson,
  • Regina Brunauer,
  • Larry J. Suva,
  • Manjong Han,
  • Connor P. Dolan,
  • Ken Muneoka

摘要

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.