Osteal macrophages: A new twist on coupling during bone dynamics

Pettit, Allison R.; Chang, Ming; Hume, David; Raggatt, Liza J.

doi:10.1016/j.bone.2008.08.128

Cited by 172 publications

(135 citation statements)

References 82 publications

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“…Its role in the context of cancer and, specifically, skeletal metastases is intriguing yet unexplored. In normal bone, macrophages, known as "osteomacs," constitute one-sixth of the total cells and express specific markers: F4/80 and CD68 (37,38). Interestingly, depletion of macrophages influences osteoblastic bone formation, bone healing, and hematopoietic niche maintenance (38 -42).…”

Section: Discussionmentioning

confidence: 99%

Polarization of Prostate Cancer-associated Macrophages Is Induced by Milk Fat Globule-EGF Factor 8 (MFG-E8)-mediated Efferocytosis

Soki

Koh

Jones

et al. 2014

Journal of Biological Chemistry

150

160

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Background:The growing body of data on tumor-associated macrophages largely neglects phagocytosis of apoptotic cells. Results: MFG-E8, induced during efferocytosis, contributes to macrophage polarization with STAT3/SOCS3 pathway involvement. Conclusion: Efferocytosis induces macrophage polarization into tumor-associated macrophages mediated by MFG-E8. Significance: A novel tumor-promoting mechanism for macrophage polarization through efferocytosis and MFG-E8 and its corresponding signaling pathway were identified.

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Section: Discussionmentioning

confidence: 99%

Polarization of Prostate Cancer-associated Macrophages Is Induced by Milk Fat Globule-EGF Factor 8 (MFG-E8)-mediated Efferocytosis

Soki

Koh

Jones

et al. 2014

Journal of Biological Chemistry

150

160

View full text Add to dashboard Cite

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“…This assay measures only differentiation and activity of periosteal progenitor cells, as any mature osteoclasts that have remained in the 6 -7-day-old calvariae are lost during the pre-culture period after exposure to basic medium and indomethacin (49). These progenitors are likely to represent a distinct pool from bone marrow progenitors and may either be derived from circulating committed progenitors or represent a pool of tissue macrophages (50). Heterogeneity among osteoclasts and osteoblasts in different parts of the skeleton has been recognized during recent years (51) consistent with our own findings that ATRA is an inhibitor of RANKL-induced osteoclastogenesis in BMM cultures (52), whereas ATRA stimulates osteoclastic genes and bone resorption in mouse calvariae (59).…”

Section: Discussionmentioning

confidence: 99%

Activation of Liver X Receptor (LXR) Inhibits Receptor Activator of Nuclear Factor κB Ligand (RANKL)-induced Osteoclast Differentiation in an LXRβ-dependent Mechanism

Remen

Henning

Lerner

et al. 2011

Journal of Biological Chemistry

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Bone destruction is the major pathological process in many bone metabolic diseases and is a result of increased osteoclast formation and bone resorption. The liver X receptors (␣,␤), important regulators of cholesterol metabolism and inflammatory signaling, have recently been observed to play a role in both physiological and pathological bone turnover. However, the relationship between liver X receptors (LXR) and osteoclast differentiation/formation remains unknown. Here, we report that the LXR ligand GW3965 is able to clearly and potently inhibit the formation of mature osteoclasts from receptor activator of nuclear factor B ligand (RANKL)-stimulated human and murine osteoclast precursors. This results in a significant inhibition of bone resorption. We observed that GW3965 significantly inhibited expression of the osteoclast markers tartrateresistant acid phosphatase, cathepsin K, osteoclast-associated receptor (OSCAR), and calcitonin receptor, appearing to act in an NFATc1/p38/microphthalmia-associated transcription factor (MITF)-dependent mechanism, independently of receptor activator of nuclear factor B or c-Fos and not directly involving the NFB pathways. GW3965 was less effective in RAW264.7 monocyte/macrophage cells, which are more committed into the osteoclast lineage. Also, GW3965 seemed to act differently depending on the source of the progenitor cells as it had no effect on calvarial osteoclasts, compared with marrow or bloodderived monocytes. As these effects were abolished in osteoclast precursors derived from LXR␤ ؊/؊ mice, we suggest that GW3965 acts via an LXR␤-dependent mechanism. Taken together, our results suggest that the LXR can act as an important inhibitor of RANKL-mediated osteoclast differentiation.Bone remodeling occurs continuously throughout life to maintain bone quality in response to mechanical stress and hormonal regulation. To retain a normal bone mass, bone is resorbed by osteoclasts, and new bone matrix is deposited by osteoblasts in a tightly coupled process. Imbalances in this process can lead to excessive resorption by the osteoclasts and increased bone fragility, as observed in many common skeletal diseases (osteoporosis, metastatic bone disease, and Paget disease of bone) (1, 2). Osteoclasts are multinucleated giant cells derived from the pluripotent hematopoietic stem cell lineage. Differentiation of the precursor cells into the osteoclast lineage is principally regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NFB ligand (RANKL) 2 (3). Binding of RANKL to its receptor RANK activates different signaling cascades (NFB, MAPK, and Ca 2ϩ oscillation/calcineurin) to induce nuclear factor of activated T cells c1 (NFATc1), the key transcription factor in osteoclastogenesis (4, 5). NFATc1 in turn induces the transcription of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP/acp5), cathepsin K (ctsk), osteoclast-associated receptor (oscar), and calcitonin receptor (calcr) (6).The liver X receptors, LXR␣ and LXR␤, are me...

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“…Activated macrophages secrete BMP2 and transforming growth factor b (TGF-b). It has been shown that the discharging macrophages result in the inhibition of in vivo bone formation [65][66][67][68]. Thereby, magnesium scaffolds coated with -TCP showed desired osteogenesis over osteoclastogenesis, due to the upregulation of osteoinductive molecules secreted by macrophages in contact with -TCP coating [63].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%