title: Absence of bone sialoprotein (BSP) alters profoundly hematopoiesis and upregulates osteopontin.
abstract: Matrix proteins of the SIBLING family interact with bone cells, extracellular matrix and mineral and are thus in a key position to regulate the microenvironment of the bone tissue, including its hematopoietic component. In this respect, osteopontin (OPN) has been implicated in the hematopoietic stem cell (HSC) niche as negative regulator of the HSC function. We investigated the impact on hematopoietic regulation of the absence of the cognate bone sialoprotein (BSP). BSP knockout (-/-) mice display increased bone marrow cellularity, and an altered commitment of hematopoietic precursors to myeloid lineages, leading in particular to an increased frequency of monocyte/macrophage cells. The B cell pool is increased in -/- bone marrow, and its composition is shifted toward more mature lymphocyte stages. BSP-null mice display a decreased HSC fraction among LSK cells and a higher percentage of more committed progenitors as compared to +/+. The fraction of proliferating LSK progenitors is higher in -/- mice, and after PTH treatment the mutant HSC pool is lower than in +/+. Strikingly, circulating levels of OPN as well as its expression in the bone tissue are much higher in the -/-. Thus, a BSP-null bone microenvironment affects the hematopoietic system both quantitatively and qualitatively, in a manner in part opposite to the OPN knockout, suggesting that the effects might in part reflect the higher OPN expression in the absence of BSP.
authors.affiliation: INSERM U1059/LBTO, Université Jean Monnet-Université de Lyon, Saint-Étienne, France.
authors.forename: Renata Neves
authors.initials: RN
authors.lastname: Granito
authors.forename: Wafa
authors.initials: W
authors.lastname: Bouleftour
authors.forename: Odile
authors.initials: O
authors.lastname: Sabido
authors.forename: Chloé
authors.initials: C
authors.lastname: Lescale
authors.forename: Mireille
authors.initials: M
authors.lastname: Thomas
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
authors.forename: Michèle
authors.initials: M
authors.lastname: Goodhardt
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D058574:Integrin-Binding Sialoprotein / Q000172:deficiency* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis / Q000502:physiology; D053495:Osteopontin / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D058574:Integrin-Binding Sialoprotein; D053495:Osteopontin