Hematopoietic Stem Cells Regulate Mesenchymal Stromal Cell Induction into Osteoblasts Thereby Participating in the Formation of the Stem Cell Niche

Jung, Younghun; Song, Junhui; Shiozawa, Yusuke; Wang, Jingcheng; Wang, Zhuo; Williams, Benjamin; Havens, Aaron M.; Schneider, Abraham; Ge, Chunxi; Franceschi, Renny T.; McCauley, Laurie K.; Krebsbach, Paul H.; Taichman, Russell S.

doi:10.1634/stemcells.2008-0149

Cited by 159 publications

(130 citation statements)

References 58 publications

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“…In 2008, they showed that hematopoietic stem cells (HSCs) are capable of inducing osteogenic differentiation of murine MSCs via paracrine stimulation with bone morphogenetic protein 2 and 6 (BMP-2, BMP-6) (Jung et al 2008). This finding was substantiated in a subsequent paper which demonstrated that EPO activates JAK/STAT signaling in HSCs leading to BMP secretion (Shiozawa et al 2010).…”

Section: Epo and Bonementioning

confidence: 99%

The effect of erythropoietin on bone

Rölfing¹

2014

Acta Orthopaedica

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Section: Epo and Bonementioning

confidence: 99%

The effect of erythropoietin on bone

Rölfing¹

2014

Acta Orthopaedica

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“…It has been published previously that they may arise from bone marrow cells [12], endothelial cells [19], or muscle stem cells [45]. In answer to the questions posed by us in these studies: (1) yes, osteoprogenitors are derived from progenitors in the endoneurium of peripheral nerves.…”

Section: Discussionmentioning

confidence: 99%

Osteoblasts Have a Neural Origin in Heterotopic Ossification

Lazard

Olmsted-Davis

Salisbury

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Heterotopic ossification (HO) is the process of bone formation at a nonskeletal site. Recently, we showed that the earliest steps occur in sensory nerves. We now extend these studies by identifying unique osteogenic progenitors within the endoneurial compartment of sensory nerves. Questions/purposes We asked: (1) What is the nature of the osteoprogenitor in the endoneurium of peripheral nerves? (2) How do osteoprogenitors travel from the nerve to the site of new bone formation? Methods HO was induced by intramuscular injection of Ad5BMP-2-transduced cells in mice. Osteoprogenitors were identified through immunohistochemistry and then quantified and further characterized by fluorescence-activated cell sorting and immunocytochemistry. The kinetics of the appearance of markers of extravasation was determined by quantitative reverse transcription-polymerase chain reaction. In each experiment mice were injected with bone morphogenetic protein-2 (BMP-2)-producing cells (experimental) or with cells transduced with empty vector or, in some cases, a group receiving no injection (control). Results Induction of HO leads to the expression, within 24 hours, of osteoblast-specific transcription factors in cells in the endoneurium followed by their coordinate disappearance from the nerve at 48 hours. They reappear in 123Clin Orthop Relat Res (2015) 473:2790-2806 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® blood also at 48 hours after induction. During vessel entrance they begin to express the tight junction molecule, claudin 5. The cells expressing both the osteoblast-specific transcription factor, osterix, as well as claudin 5, then disappear from circulation at approximately 3 to 4 days by extravasation into the site of new bone formation. These endoneurial osteoprogenitors express neural markers PDGFRa, musashi-1, and the low-affinity nerve growth factor receptor p75(NTR) as well as the endothelial marker Tie-2. In a key experiment, cells that were obtained from mice that were injected with cells transduced with an empty vector, at 2 days after injection, contained 0.83% (SD, 0.07; 95% confidence interval [CI], 0.59-1.05) cells expressing claudin 5. However, cells that were obtained from mice 2 days after injection of BMP-2-producing cells contained 4.5% cells expressing claudin 5 (SD, 0.72%; 95% CI, 2.01-6.94; p \ 0.0015). Further analysis revealed that all of the cells expressing claudin 5 were found to be positive for osteoblast-specific markers, whereas cells not expressing claudin 5 were negative for these same markers. Conclusions The findings suggest that the endoneurial progenitors are the major osteogenic precursors that are used for HO. They exit the nerve through the endoneurial vessels, flow through vessels to the site of new bone formation, and then extravasate out of the vessels into this site. Clinical Relevance The biogenesis of osteoblasts in HO is very different than expected and shows that HO is, at least in par...

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“…EMSA ERITIN contains beneficial natural compounds such as genistein, cytokinin, nicotinic acid, pantothenic acid, biotin, riboflavin, folic acid, thiamine, thymus, and brain [16], stromal cells [17], osteoblasts [18], immune cells, blood vessels, and heart. The main physiological function of the interaction SDF1/CXCR4 is set homing, storage, and defense of hematopoietic stem cells and progenitor cells that are still primitive [19].…”

Section: Discussionmentioning

confidence: 99%

Polyherbal EMSA ERITIN Promotes Erythroid Lineages and Lymphocyte Migration in Irradiated Mice

2016

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Radiotherapy is commonly used to kill malignant cells, but it can significantly deplete hematopoietic and splenic erythroblasts. Radioprotective agents are therefore very important in clinical radiotherapy. We examined the effect of poly-herbal EMSA ERITIN on immunological responses when administered to sublethally irradiated mice with the aim of highlighting promotes erythroid lineages and lymphocytes migration in irradiated mice with the parameter are TER119+CD123+in bone marrow and SDF-1 in bone marrow and spleen organ. Normal BALB/c mice were sublethally irradiated with 600 rad. EMSA ERITIN was administered orally at different doses:(1.04, 3.125 and 9.375 mg/g body weight) for 15 days. On day 16 erythroid lineages (TER-119+CD123+) were observed in bone marrow and lymphocytes migration by the production of SDF-1 in spleen and bone marrow. Lymphocytes migration was indicated by the production of SDF-1 in spleen and bone marrow using flow cytometry analysis. EMSA ERITIN increased the generation of erythroid lineage cells marked by TER119+CD123+ and promoted lymphocyte migration by increasing SDF-1 production in bone marrow and spleen. EMSA ERITIN appears to be a powerful medicinal herb with potential as a food supplement to normalize homeostasis and erythropoiesis after radiation.

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Hematopoietic Stem Cells Regulate Mesenchymal Stromal Cell Induction into Osteoblasts Thereby Participating in the Formation of the Stem Cell Niche

Cited by 159 publications

References 58 publications

The effect of erythropoietin on bone

The effect of erythropoietin on bone

Osteoblasts Have a Neural Origin in Heterotopic Ossification

Polyherbal EMSA ERITIN Promotes Erythroid Lineages and Lymphocyte Migration in Irradiated Mice

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