Defective Osteogenesis of the Stromal Stem Cells Predisposes CD18-Null Mice to Osteoporosis

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 pr...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-09, Vol.102 (39), p.14022-14027
Main Authors: Miura, Yasuo, Miura, Masako, Gronthos, Stan, Allen, Matthew R., Cao, Chunzhang, Uveges, Thomas E., Bi, Yanming, Ehirchiou, Driss, Kortesidis, Angela, Shi, Songtao, Zhang, Li, Prockop, Darwin J.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Bone and Bones - cytology
Bone formation
Bone marrow
Bone Marrow Cells - cytology
Bone Marrow Cells - immunology
Bone Marrow Cells - physiology
Bones
CD18 Antigens - analysis
CD18 Antigens - genetics
CD18 Antigens - metabolism
Cell adhesion
Cell adhesion & migration
Cell Differentiation
Cell Proliferation
Integrins
Leukocytes
Mice
Osteoclasts
Osteoclasts - physiology
Osteogenesis - genetics
Osteoporosis
Osteoporosis - genetics
Rodents
Stem cells
Stem Cells - cytology
Stem Cells - immunology
Stem Cells - physiology
Stromal Cells - cytology
Stromal Cells - immunology
Stromal Cells - physiology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0409397102