Abstract:
:Although recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche, the mechanisms underpinning this remain to be fully defined. The studies described herein examine the role in hematopoiesis of Osteopontin (Opn), a multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized critical role for Opn in regulation of the physical location and proliferation of HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC transmarrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSCs in Opn-/- mice after transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via beta1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPCs in vitro, the physiologic relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn-/- mice. These data therefore provide strong evidence that Opn is an important component of the HSC niche which participates in HSC location and as a physiologic-negative regulator of HSC proliferation.
journal_name
Bloodjournal_title
Bloodauthors
Nilsson SK,Johnston HM,Whitty GA,Williams B,Webb RJ,Denhardt DT,Bertoncello I,Bendall LJ,Simmons PJ,Haylock DNdoi
10.1182/blood-2004-11-4422subject
Has Abstractpub_date
2005-08-15 00:00:00pages
1232-9issue
4eissn
0006-4971issn
1528-0020pii
2004-11-4422journal_volume
106pub_type
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