Impact of maturational status on the ability of osteoblasts to enhance the hematopoietic function of stem and progenitor cells

Cheng, Ying; Chitteti, Brahmananda R.; Streicher, Drew A.; Morgan, Joseph A.; Rodriguez-Rodriguez, Sonia; Carlesso, Nadia; Srour, Edward F.; Kacena, Melissa A.

doi:10.1002/jbmr.302

Cited by 39 publications

(60 citation statements)

References 71 publications

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“…CD166 expression on Stro-1 1 stromal cells 9 and binding of hematopoietic cells via CD166 to a yolk sacderived stromal cell line were also demonstrated. 10 These, and our data 2,4,5,11 confirmed that CD166 is expressed on hematopoietic progenitors and on OB, suggesting the unique possibility that these cells may interact with one another through CD166-CD166 interactions.…”

Section: Introductionsupporting

confidence: 73%

CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche

Chitteti¹,

Kobayashi²,

Cheng³

et al. 2014

Blood

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Section: Introductionsupporting

confidence: 73%

CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche

Chitteti¹,

Kobayashi²,

Cheng³

et al. 2014

Blood

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“…Two studies have suggested that HSC-supporting cells are osteocalcin ϩ osteoblasts, based on immunofluorescence data demonstrating the proximity of HSCs to these cells. 18,27 Several studies have recently isolated cells of the osteoblastic lineage [28][29][30] and, whereas some results have suggested that hematopoietic progenitors are preferentially supported by immature osteoblastic cells, 29,31 others found that multiple fractions within the osteoblastic lineage could support HSCs, at least in vitro. 28,30 Data on the effects of osteoblastic deficiency induced in a transgenic mouse model expressing herpesvirus thymidine kinase gene under the control of a 2.3-kb fragment of the rat collagen-␣1 type I gene promoter suggest that osteoblastic cells targeted by this promoter, as well as their osteoblastic and osteocytic progeny, comprise the pool of osteoblastic cells capable of HSC regulation and support.…”

Section: Discussionmentioning

confidence: 99%

“…28,30 Data on the effects of osteoblastic deficiency induced in a transgenic mouse model expressing herpesvirus thymidine kinase gene under the control of a 2.3-kb fragment of the rat collagen-␣1 type I gene promoter suggest that osteoblastic cells targeted by this promoter, as well as their osteoblastic and osteocytic progeny, comprise the pool of osteoblastic cells capable of HSC regulation and support. 32 Ex vivo coculture systems designed to specifically identify HSC-supportive cell subsets [28][29][30][31] have not been evaluated for osteocytic signals and, given the mode and duration of coculture, are not likely to include osteocytic-type cells. Because, in TG mice, the osteocyte population is greatly expanded 8 and HSC support is decreased, the results of the current study also suggest that osteocytes are likely not a regulatory component of the HSC niche.…”

Section: Discussionmentioning

confidence: 99%

Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells

Calvi

Bromberg

Rhee³

et al. 2012

Blood

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Microenvironmental expansion of hematopoietic stem cells (HSCs) is induced by treatment with parathyroid hormone (PTH)or activation of the PTH receptor (PTH1R) in osteoblastic cells; however, the osteoblastic subset mediating this action of PTH is unknown. Osteocytes are terminally differentiated osteoblasts embedded in mineralized bone matrix but are connected with the BM. Activation of PTH1R in osteocytes increases osteoblastic number and bone mass. To establish whether osteocyte-mediated PTH1R signaling expands HSCs, we studied mice expressing a constitutively active PTH1R in osteocytes (TG mice IntroductionTo survive throughout the life of an individual, hematopoietic stem cells (HSCs) must balance self-renewal and differentiation. 1 This essential regulation of stem cells is thought to be determined at least in part by the environment, or niche, in which these cells reside. 2 Hormonal stimulation by parathyroid hormone (PTH) results in HSC expansion through the niche, 3 but the PTH receptor (PTH1R) is not expressed in HSCs. 4 In the BM microenvironment, PTH1R is expressed in cells in the osteoblastic lineage, including Nestin ϩ cells, thought to represent mesenchymal stem cells (MSCs), which recent data suggest are regulatory components of the HSC niche. 5 Because PTH treatment expands the Nestin ϩ cell pool and causes it to more rapidly differentiate into its progeny, 5 it is not known which cells in the mesenchymal/osteoblastic lineage are responsible for the PTH-dependent signals that result in HSC expansion. We have demonstrated previously that expression of a constitutively active PTH receptor (caPTH1R) in immature and mature osteoblasts was sufficient to expand HSCs. 3 Therefore, the cell population capable of initiating microenvironmental changes that expand HSCs must comprise osteoblastic cells targeted by the 2.3-kb fragment of the mouse collagen I gene promoter (hereafter referred to as 2.3Col1 osteoblastic cells) and their progeny, which includes osteocytic cells.It was demonstrated recently that PTH stimulates osteocytes, in which activation of PTH1R signaling down-regulates the expression of the Wnt antagonist Sclerostin. 6 This effect of PTH on Sclerostin has also been demonstrated in postmenopausal women treated with PTH, 7 suggesting that Sclerostin down-regulation may be an important mediator of the bone anabolic action of PTH.Using an in vivo model in which a constitutively active PTH1R is targeted to osteocytes (dentin matrix protein-1 [DMP1]-caPTH1R mice, hereafter referred to as TG mice), we demonstrated that PTH-dependent signals in osteocytes control bone mass and bone remodeling. 8 Osteocytes are former osteoblasts buried into bone matrix but connected to the endosteum via cytoplasmic processes, 9 which sense mechanical stimuli and regulate both osteoblastic and osteoclastic numbers. 10 It was unknown whether osteocytes affect hematopoiesis and/or HSCs. In the present study, we examined whether signaling downstream of the PTH1R in osteocytes supports the expansion of HSCs by analyzi...

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“…That basal Prg4 mRNA expression was higher in less differentiated osteoblastic cell cultures suggests that more immature osteoblastic cells are a primary source of proteoglycan 4 in the bone marrow. Considering that more immature osteoblastic cells have been implicated in HPC expansion and function, 43 the finding that basal Prg4 mRNA expression is higher in less differentiated osteoblastic cell cultures suggests that proteoglycan 4 may be involved in the mechanism by which more immature osteoblastic cells support HPCs.…”

Section: Discussionmentioning

confidence: 99%

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells

Novince¹,

Koh²,

Michalski³

et al. 2011

The American Journal of Pathology

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Proteoglycan 4 (PRG4), a critical protective factor in articular joints, is implicated in hematopoietic progenitor cell expansion and megakaryopoiesis. PRG4 loss-of-function mutations result in camptodactyly-arthropathy-coxa varapericarditis (CACP) syndrome, which is characterized primarily by precocious joint failure. PRG4 was identified as a novel parathyroid hormone (PTH) responsiveness gene in osteoblastic cells in bone, and was investigated as a potential mediator of PTH actions on hematopoiesis. Sixteen-week-old Prg4 ؊/؊ mutant and Prg4 ؉/؉ wild-type mice were treated daily with intermittent PTH (residues 1-34) or vehicle for 6 weeks. At 22 weeks of age, Prg4 mutant mice had increased peripheral blood neutrophils and decreased marrow B220 ؉ (B-lymphocytic) cells, which were normalized by PTH. The PTH-induced increase in marrow Lin ؊ Sca-1 ؉ c-Kit ؉ (hematopoietic progenitor) cells was blunted in mutant mice. Basal and PTHstimulated stromal cell-derived factor-1 (SDF-1) was decreased in mutant mice, suggesting SDF-1 as a candidate regulator of proteoglycan 4 actions on hematopoiesis in vivo. PTH stimulation of IL-6 mRNA was greater in mutant than in wild-type calvaria and bone marrow, suggesting a compensatory mechanism in the PTH-induced increase in marrow hematopoietic progenitor cells. In summary, proteoglycan 4 is a novel PTH-responsive factor regulating immune cells and PTH actions on marrow hematopoietic progenitor cells.

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Impact of maturational status on the ability of osteoblasts to enhance the hematopoietic function of stem and progenitor cells

Cited by 39 publications

References 71 publications

CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche

CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche

Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells

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