Expansion of the sagittal suture induces proliferation of skeletal stem cells and sustains endogenous calvarial bone regeneration.

Autor:	Aldawood ZA; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.; Department of Biomedical Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia., Mancinelli L; Department of Periodontics and Preventive Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261.; Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261., Geng X; Department of Periodontics and Preventive Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261.; Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261., Yeh SA; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114., Di Carlo R; Department of Periodontics and Preventive Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261.; Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261., C Leite T; Department of Periodontics and Preventive Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261.; Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261., Gustafson J; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101., Wilk K; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115., Yozgatian J; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115., Garakani S; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115., Bassir SH; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115., Cunningham ML; Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101.; Division of Craniofacial Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195., Lin CP; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114., Intini G; Department of Periodontics and Preventive Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261.; Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.; University of Pittsburgh UPMC Hillman Cancer Center, Pittsburgh, PA 15232.; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Apr 18; Vol. 120 (16), pp. e2120826120. Date of Electronic Publication: 2023 Apr 11.
DOI:	10.1073/pnas.2120826120
Abstrakt:	In newborn humans, and up to approximately 2 y of age, calvarial bone defects can naturally regenerate. This remarkable regeneration potential is also found in newborn mice and is absent in adult mice. Since previous studies showed that the mouse calvarial sutures are reservoirs of calvarial skeletal stem cells (cSSCs), which are the cells responsible for calvarial bone regeneration, here we hypothesized that the regenerative potential of the newborn mouse calvaria is due to a significant amount of cSSCs present in the newborn expanding sutures. Thus, we tested whether such regenerative potential can be reverse engineered in adult mice by artificially inducing an increase of the cSSCs resident within the adult calvarial sutures. First, we analyzed the cellular composition of the calvarial sutures in newborn and in older mice, up to 14-mo-old mice, showing that the sutures of the younger mice are enriched in cSSCs. Then, we demonstrated that a controlled mechanical expansion of the functionally closed sagittal sutures of adult mice induces a significant increase of the cSSCs. Finally, we showed that if a calvarial critical size bone defect is created simultaneously to the mechanical expansion of the sagittal suture, it fully regenerates without the need for additional therapeutic aids. Using a genetic blockade system, we further demonstrate that this endogenous regeneration is mediated by the canonical Wnt signaling. This study shows that controlled mechanical forces can harness the cSSCs and induce calvarial bone regeneration. Similar harnessing strategies may be used to develop novel and more effective bone regeneration autotherapies.
Databáze:	MEDLINE
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