biostudies-literatureUnknown13Broussard J<h4>Introduction</h4>Bone regeneration following injury depends on osteoprogenitor cells derived predominantly from the periosteum. Incomplete regeneration has been attributed to both cell-extrinsic factors (e.g., environment, inflammation, mechanical instability) and cell-intrinsic factors (e.g., impaired proliferation or differentiation of stem cells). In the digit amputation mouse model, amputation through the third phalanx (P3) supports complete regeneration, while amputation through the second phalanx (P2) results in callus formation and scarring. Periosteal cells are known to be the major contributing cell source for repair and regeneration. Yet the healing outcomes of P2 and P3 amputations are significantly different. This study tests whether P2 and P3 cells are functionally equivalFrontiers in cell and developmental biology1684670https://www.ebi.ac.uk/biostudies/studies/S-EPMC12756367biostudies-literatureOsteoprogenitor cells from non-regenerative bone show greater resistance to cellular stress than those from regenerative bone.PMC12756367Long TBroussard JSammarco MCCulpepper STower RJSimkin JTrostle AJfalseOsteoprogenitor cells from non-regenerative bone show greater resistance to cellular stress than those from regenerative bone.<h4>Introduction</h4>Bone regeneration following injury depends on osteoprogenitor cells derived predominantly from the periosteum. Incomplete regeneration has been attributed to both cell-extrinsic factors (e.g., environment, inflammation, mechanical instability) and cell-intrinsic factors (e.g., impaired proliferation or differentiation of stem cells). In the digit amputation mouse model, amputation through the third phalanx (P3) supports complete regeneration, while amputation through the second phalanx (P2) results in callus formation and scarring. Periosteal cells are known to be the major contributing cell source for repair and regeneration. Yet the healing outcomes of P2 and P3 amputations are significantly different. This study tests whether P2 and P3 cells are functionally equival2025-01-01T00:00:00Z20252026-06-09T03:17:28.174Z2026-06-09T03:08:01.925ZS-EPMC127563674148799910.3389/fcell.2025.1684670