Comparison of skeletal and soft tissue pericytes identifies CXCR4+ bone forming mural cells in human tissues

Jiajia Xu, Dongqing Li, Ching Yun Hsu, Ye Tian, Leititia Zhang, Yiyun Wang, Robert J. Tower, Leslie Chang, Carolyn A. Meyers, Yongxing Gao, Kristen Broderick, Carol Morris, Jody E. Hooper, Sridhar Nimmagadda, Bruno Péault, Aaron W. James

Research output: Contribution to journalArticlepeer-review

Abstract

Human osteogenic progenitors are not precisely defined, being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells (MSCs). Notably, select human pericytes can develop into bone-forming osteoblasts. Here, we sought to define the differentiation potential of CD146+ human pericytes from skeletal and soft tissue sources, with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte. CD146+CD31CD45 pericytes were derived by fluorescence-activated cell sorting from human periosteum, adipose, or dermal tissue. Periosteal CD146+CD31CD45 cells retained canonical features of pericytes/MSC. Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo, while soft tissue pericytes did not readily. Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts, and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes. Conversely, enrichment of CXCR4+ pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell. In sum, human skeletal and soft tissue pericytes differ in their basal abilities to form bone. Diversity exists in soft tissue pericytes, however, and CXCR4+ pericytes represent an osteoblastogenic, non-adipocytic cell precursor. Indeed, enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.

Original languageEnglish (US)
Article number22
JournalBone Research
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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