Defective osteogenesis of the stromal stem cells predisposes CD18-null mice to osteoporosis

Yasuo Miura, Masako Miura, Stan Gronthos, Matthew R. Allen, Chunzhang Cao, Thomas E. Uveges, Yanming Bi, Driss Ehirchiou, Angela Kortesidis, Songtao Shi, Li Zhang

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Osteogenesis by the bone marrow stromal stem cells (BMSSCs) supports continuous bone formation and the homeostasis of the bone marrow microenvironment. The mechanism that controls the proliferation and differentiation of BMSSCs is not fully understood. Here, we report that CD18, a surface protein present primarily on hematopoietic cells, but not on differentiated mesenchymal cells, is expressed by the stromal stem cells and plays a critical role in the osteogenic process. Constitutive expression of CD18 on BMSSCs using a retroviral promoter significantly enhances bone formation in vivo, whereas genetic inactivation of CD18 in mice leads to defective osteogenesis due to decreased expression of the osteogenic master regulator Runx2/Cbfa1. The defective osteogenesis of the CD18-null BMSSCs can be restored by expressing full-length, but not cytoplasmic domain-truncated, CD18. Radiographic analyses with dual-energy x-ray absorptiometry and 3D microcomputed tomography show that mice lacking CD18 have decreased bone mineral density and exhibit certain features of osteoporosis. Altogether, this work demonstrates that CD18 functions critically in the osteogenesis of BMSSCs, and thus lack of CD18 expression in the leukocyte adhesion deficiency patients may predispose them to osteoporosis.

Original languageEnglish
Pages (from-to)14022-14027
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number39
DOIs
Publication statusPublished - 27 Sep 2005

Keywords

  • Bone
  • Integrin
  • Leukocyte adhesion deficiency

ASJC Scopus subject areas

  • General

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