A new bone to pick: osteoblasts and the haematopoietic stem-cell niche.
Two recent publications highlight the role of bone-forming cells, the osteoblasts, in controlling the development of neighboring haematopoietic stem cells (HSCs).1,2 Using two distinct transgenic mouse models, one using the conditional deletion of the Bone Morphogenetic Protein Receptor 1A (BMPR1A) gene, the other using over-expression of an active PTH/PTHrP receptor (PPR) mutant within osteoblasts, the authors show parallel, concordant increases in the generation of trabecular osteoblasts and the number of HSCs. In situ staining showed that rarely cycling HSCs sporadically attach to endosteal osteoblasts, while in vitro assays indicated that ligation of Jag1 on osteoblasts by Notch1 on HSCs promotes HSC proliferation. These two independent works have revived and revitalized the notion that osteoblasts are a major, defining component of the HSC niche within the bone marrow (BM). This minireview discusses these results in the context of other recent studies of mesenchymal cells within the BM microenvironment, presents one potential unified model of the functional anatomy of the BM HSC niche, and highlights new questions raised by these and other studies of osteoblasts and HSCs.
Zhu
Jiang
J
Departments of Medicine and Pediatrics, and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Emerson
Stephen G
SG
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I; D002455:Cell Division; D017353:Gene Deletion; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics; D014157:Transcription Factors
C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D010281:Parathyroid Hormone; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C498211:BMPR1A protein, human; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I