Publication Date
9-26-2025
Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms26199413
PMID
41096681
PMCID
PMC12525401
PubMedCentral® Posted Date
9-26-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Calvarial suture skeletal stem cells (Su-SSCs) are a distinct stem cell population for craniofacial bone formation by intramembranous ossification, compared to long bone periosteal SSCs (LB-PSSCs) with endochondral (osteochondrogenic) ossification. However, whether SSC intrinsic or extrinsic factors affect their differentiation process has not been well elucidated. Here, using an inducible Prx1-CreER-EGFP+/−;Rosa26-tdTomato mouse model, we observed that endogenous Prx1+ Su-SSCs and their orthotopic transplantation into calvarial injury do not form cartilage intermediates at the injury sites, while the transplantation of Prx1+ LB-PSSCs into LB injury induces osteochondrogenic differentiation, respectively. However, the heterotopic transplantation of Prx1+ Su-SSCs (Su-SSCs into LB injury) showed some surprising findings that the transplanted Su-SSCs acquire new chondrocyte differentiation properties at the LB injury sites, although the heterotopic-transplanted Prx1+ LB-PSSCs maintained their endochondral ossification properties at the calvarial injury sites. Further, a comparative single-cell transcriptomic analysis of LB-PSSCs and Su-SSCs revealed that Su-SSCs express a higher set of anti-chondrogenic genes, such as Wnt5b, Twist1 while LB-PSSCs highly express chondrogenic Hoxa-9, Hoxc-9, Hoxa-10, Hoxc-10, and Comp genes. We also found that the heterotopic transplantation of LB-PSSCs into calvarial injury enhances bone healing in vivo. Taken together, these findings suggest that LB-PSSCs have high regenerative capability with invariable endochondral ossification even after the heterotopic transplantation but Su-SSCs are more flexible and regulated by the local bone environment. The transplantation of periosteal SSCs will be a promising method for large craniofacial bone defects.
Keywords
Animals, Bone Regeneration, Skull, Mice, Cell Differentiation, Osteogenesis, Homeodomain Proteins, Stem Cells, Chondrogenesis, suture stem cells, skeletal stem cells, cell transplantation, craniomaxillofacial, Prx1, chondrogenesis
Published Open-Access
yes
Recommended Citation
Solidum, Jea; Yamasaki, Kohei; Jeong, Youngjae; et al., "Distinct Intrinsic and Extrinsic Factors Differentially Regulate Skeletal Stem Cells in Calvaria Versus Long Bones During Bone Regeneration" (2025). Faculty and Staff Publications. 5082.
https://digitalcommons.library.tmc.edu/baylor_docs/5082
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