title: Defective osteogenesis of the stromal stem cells predisposes CD18-null mice to osteoporosis.
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.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Rockville, MD 20855, USA.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.forename: Masako
authors.initials: M
authors.lastname: Miura
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Allen
authors.forename: Chunzhang
authors.initials: C
authors.lastname: Cao
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Uveges
authors.forename: Yanming
authors.initials: Y
authors.lastname: Bi
authors.forename: Driss
authors.initials: D
authors.lastname: Ehirchiou
authors.forename: Angela
authors.initials: A
authors.lastname: Kortesidis
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology; D018821:CD18 Antigens / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D051379:Mice; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology
chemical_list: D018821:CD18 Antigens