Oxygen saturation in the bone marrow of healthy volunteers

Harrison, Jonathan S.; Rameshwar, Pranela; Chang, Victor; Bandari, Persis

doi:10.1182/blood.v99.1.394

Cited by 284 publications

(205 citation statements)

References 4 publications

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“…With the exception of respiratory epithelia, most cells are not normally exposed to such high PO 2 in vivo. Measurements of PO 2 in marrow aspirates (Ishikawa and Ito, 1988;Harrison et al, 2002) may yield misleadingly high average values (6.2-6.6%) because haematopoietic cells in vivo are arranged in clusters around sinusoids, such that some cells may be located as many as 10 cell diameters away from the nearest vascular channel. Modeling studies of the intact marrow indicate that many haematopoietic cells, particularly the most primitive progenitors, are probably located in a very low PO 2 environment (Chow et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…In normal tissues, interstitial PO 2 is roughly in the range 4-8%. Measurements, for example, of bone marrow aspirates from normal volunteer donors yielded mean PO 2 values of 6.2% (Ishikawa and Ito, 1988) and 6.6% (Harrison et al, 2002). In environments such as the poorly vascularized yellow fatty bone marrow of the very elderly, or in inflamed tissue, infected tissue, tumors, wounds, and fracture sites, PO 2 could be considerably lower.…”

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confidence: 99%

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Hypoxia is a major stimulator of osteoclast formation and bone resorption

Arnett

Gibbons

Utting

et al. 2003

Journal Cellular Physiology

269

204

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Hypoxia is known to act as a general stimulator of cells derived from marrow precursors. We investigated the effect of oxygen tension on the formation and function of osteoclasts, the cells responsible for bore resorption, which are of promonocytic origin. Using 7-and 13-day cultures of mouse marrow cells on ivory discs, we found that reducing oxygen tension from the ambient atmospheric level of 20% by increasing the proportion of nitrogen caused progressive increases in the formation of multinucleated osteoclasts and resorption pits. Peak effects occurred in 2% oxygen, where stimulations of resorption up to 21-fold were measured. Significant stimulations of osteoclast formation and resorption were observed even in severely hypoxic cultures gassed with 0.2% oxygen. Short-term cultures of cells disaggregated from rat bones indicated that hypoxia did not alter the resorptive activity of mature osteoclasts, but reduced their survival or adherence. In 3-day organ cultures of mouse calvarial bones, exposure to 2% oxygen resulted in maximal, fivefold stimulation of osteoclast-mediated calcium release, an effect equivalent to that of prostaglandin E 2 (PGE 2 ), a reference osteolytic agent. Hypoxia also caused a moderate acidosis in calvarial cultures, presumably as a result of increased anaerobic metabolism; this observation is significant because osteoclast activation is dependent on extracellular acidification. Our experiments reveal a previously-overlooked mechanism of considerable potential importance for the regulation of bone destruction. These findings may help explain the bone loss associated with a wide range of pathological states involving local or systemic hypoxia, and emphasize the importance of the vasculature in bone.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hypoxia is a major stimulator of osteoclast formation and bone resorption

Arnett

Gibbons

Utting

et al. 2003

Journal Cellular Physiology

269

204

View full text Add to dashboard Cite

show abstract

“…Myeloma cells grow in a hypoxic microenvironment. Myeloma BM has relatively low pO 2 and sO 2 as compared with healthy subjects [113]. It has also been reported that there is no significant difference in the reduced BM pO 2 and sO 2 in MM patients as compared with MGUS patients [112].…”

Section: Hypoxia and Hypoxia-inducible Factor-1 In Myeloma-induced Anmentioning

confidence: 95%

“…However, in a MM mouse model it has been reported that both normal and MM-infiltrated BM are hypoxic, although the level of oxygen was lower in MM BM [104]. This discrepancy could be due either to the different method used in the detection of hypoxia or to the lower physiological oxygen tension reported in mice as compared to human [112][113][114].…”

Section: Hypoxia and Hypoxia-inducible Factor-1 In Myeloma-induced Anmentioning

confidence: 99%

Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

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The bone marrow microenvironment in multiple myeloma is characterized by an increased microvessel density. The production of pro-angiogenic molecules is increased and the production of angiogenic inhibitors is suppressed, leading to an "angiogenic switch". Here we present an overview of the role of angiogenesis in multiple myeloma, the pro-angiogenic factors produced by myeloma cells and the microenvironment, and the mechanisms involved in the myeloma-induced angiogenic switch. Current data suggest that the increased bone marrow angiogenesis in multiple myeloma is due to the aberrant expression of angiogenic factors by myeloma cells, the subsequent increase in pro-angiogenic activity of normal plasma cells as a result of myeloma cell angiogenic activity, and the increased number of plasma cells overall. Hypoxia also contributes to the angiogenic properties of the myeloma marrow microenvironment. The transcription factor hypoxia-inducible factor-1α is overexpressed by myeloma cells and affects their transcriptional and angiogenic profiles. In addition, potential roles of the tumor suppressor gene inhibitor of growth family member 4 and homeobox B7 have also been recently highlighted as repressors of angiogenesis and pro-angiogenic related genes, respectively. This complex pathogenetic model of myeloma-induced angiogenesis suggests that several proangiogenic molecules and related genes in myeloma cells and the microenvironment are potential therapeutic targets.

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“…The actual concentration of oxygen inside of the osteocyte lacunae during skeletal unloading remains unknown. A previous study has measured pO 2 values of approximately 6% in normal human bone marrow aspirates (46). On the basis of this information, 1% O 2 was selected as the hypoxic condition and 20% O 2 as the normoxic condition (representing the atmospheric A B oxygen levels); although it is widely accepted that a pO 2 of 20% corresponds to hyperoxia (44).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia mediates osteocyte ORP150 expression and cell death in vitro

Montesi

Jähn

Bonewald

et al. 2016

Molecular Medicine Reports

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Abstract. Skeletal unloading leads to hypoxia in the bone microenvironment, resulting in imbalanced bone remodeling that favors bone resorption. Osteocytes, the mechanosensors of bone, have been demonstrated to orchestrate bone homeostasis. Hypoxic osteocytes either undergo apoptosis or actively stimulate osteoclasts to remove bone matrix during hypoxia. Oxygen-regulated protein 150 (ORP150) is an endoplasmic reticulum-associated chaperone that has been observed to serve an important role in the cellular adaptation to hypoxia and in preventing cellular apoptosis in various tissue types. The current study hypotheses that expression of ORP150 would be increased in osteocytes under hypoxic conditions (1% O 2 ). The MLO-Y4 osteocyte cell line was cultured under normoxic or hypoxic conditions for up to 72 h. It was demonstrated that 1% O 2 significantly induced hypoxia after 16 h and up to 72 h, significantly reduced cell number at 8 and 48 h, induced cell death at 8, 24 and 48 h and induced apoptosis at 16, 24 and 48 h. Significant differences in ORP150 mRNA were observed at 72 h, however no differences were observed in the protein expression levels. The relative increase in ORP150 mRNA observed in hypoxia, compared with normoxia, may support its cytoprotective role in oxygen-deprived conditions.

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Oxygen saturation in the bone marrow of healthy volunteers

Cited by 284 publications

References 4 publications

Hypoxia is a major stimulator of osteoclast formation and bone resorption

Hypoxia is a major stimulator of osteoclast formation and bone resorption

Angiogenesis and Multiple Myeloma

Hypoxia mediates osteocyte ORP150 expression and cell death in vitro

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