Identification of LRP1+CD13+ Human Periosteal Stem Cells That Require LRP1 for Bone Repair

Authors

Youngjae Jeong
Lorenzo Deveza
Laura Ortinau
Kevin Lei
John R Dawson
Dongsu Park

Publication Date

11-22-2024

Journal

JCI Insight

DOI

10.1172/jci.insight.173831

PMID

39405183

PMCID

PMC11601900

PubMedCentral® Posted Date

11-22-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Periosteum, Animals, Mice, Low Density Lipoprotein Receptor-Related Protein-1, Stem Cells, Bone Regeneration, Male, Female, Osteogenesis, Cell Proliferation, Adult stem cells, Human stem cells, Bone biology, Stem cells

Abstract

Human periosteal skeletal stem cells (P-SSCs) are critical for cortical bone maintenance and repair. However, their in vivo identity, molecular characteristics, and specific markers remain unknown. Here, single-cell sequencing revealed human periosteum contains SSC clusters expressing known SSC markers, podoplanin (PDPN) and PDGFRA. Notably, human P-SSCs, but not bone marrow SSCs, selectively expressed identified markers low density lipoprotein receptor-related protein 1 (LRP1) and CD13. These LRP1+CD13+ human P-SSCs were perivascular cells with high osteochondrogenic but minimal adipogenic potential. Upon transplantation into bone injuries in mice, they preserved self-renewal capability in vivo. Single-cell analysis of mouse periosteum further supported the preferential expression of LRP1 and CD13 in Prx1+ P-SSCs. When Lrp1 was conditionally deleted in Prx1 lineage cells, it led to severe bone deformity, short stature, and periosteal defects. By contrast, local treatment with an LRP1 agonist at the injury sites induced early P-SSC proliferation and bone healing. Thus, human and mouse periosteum contains unique osteochondrogenic stem cell subsets, and these P-SSCs express specific markers, LRP1 and CD13, with a regulatory mechanism through LRP1 that enhances P-SSC function and bone repair.