Characterization of the BMP2-Specific Regeneration Window in the Adult Mouse Middle Phalanx Model of Induced Bone Regeneration
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Mammalian regeneration capabilities are amputation-level-dependent; amputations of the terminal phalanx (P3) initiate regeneration mediated by a blastema, while amputations transecting more proximal levels of the digit fail to regenerate, resulting in bone truncation at the amputation plane and soft tissue scarring. Therefore, what distinguishes limb bone regeneration from scar formation is the blastema, a transient population of proliferating cells that regenerate the missing structures. The adjacent bone, the middle phalanx (P2), is non-regenerative after amputation. P2 can be induced to regenerate after treatment with Bone Morphogenetic Protein 2 (BMP2), however, the bone regeneration response is dependent on the timeframe after injury in which BMP2 is applied. This timeframe is called the Regeneration Window (RW). Utilizing adult mice, our objective was to characterize a pro-regenerative wound environment that supports limb regeneration in mammals. Using immunohistochemistry, we compared the P2 RW at 9 days post amputation (9 DPA), and the P2 timeframe when the RW is closed (24 DPA), with the known regeneration-permissive characteristics of the 9 DPA P3 blastema. We report that both the 9 DPA P3 blastema and the 9 DPA P2 wound site share regeneration characteristics such as an absence of vasculature, robust proliferation, and the presence of progenitor cells. Conversely, the 24 DPA P2 wound site, when the RW is closed, is characterized by the presence of vasculature, minor proliferation, and the maturation of progenitor cells. Taken together, the 9 DPA P3 blastema and the 9 DPA P2 wound site share the presence of progenitor cells that pattern the final bone structure; however, while P3 progenitors are localized distal to the amputation plane and therefore result in a patterned regenerate, the P2 progenitors, in contrast, are circumferentially located and thus the wound site lacks the appropriate cues to pattern a regenerative response.
Nunez, Stacy A; Hall, Patrick; Muhammad, Dania Fatima (2020). Characterization of the BMP2-Specific Regeneration Window in the Adult Mouse Middle Phalanx Model of Induced Bone Regeneration. Undergraduate Research Scholars Program. Available electronically from