Increasing membrane-bound MCSF does not enhance OPGL-driven osteoclastogenesis from marrow cells

Fan, Xian; Fan, Dongjie; Gewant, H.; Royce, C. L.; Nanes, Mark S.; Rubin, Janet

doi:10.1152/ajpendo.2001.280.1.e103

Cited by 14 publications

(11 citation statements)

References 38 publications

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“…Thus, the stimulation of bone resorption during the anabolic protocol should be a transient event preceding osteoblastic bone formation to provide new remodeling sites for new incoming osteoblasts. As mentioned earlier, it is well documented that the increase in osteoclast formation is directly proportional to the level of RANKL expression, and M-CSF plays primarily a permissive role (29,32). Furthermore, both in vitro and in vivo studies have demonstrated that PTH influences osteoclast formation primarily by regulation of the RANKL/OPG ratio (33).…”

Section: Discussionmentioning

confidence: 87%

Parathyroid Hormone Stimulates Osteoblastic Expression of MCP-1 to Recruit and Increase the Fusion of Pre/Osteoclasts

Li¹,

Qin²,

Bergenstock³

et al. 2007

Journal of Biological Chemistry

194

161

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The clinical findings that alendronate blunted the anabolic effect of human parathyroid hormone (PTH) on bone formation suggest that active resorption is involved and enhances the anabolic effect. PTH signals via its receptor on the osteoblast membrane, and osteoclasts are impacted indirectly via the products of osteoblasts. Microarray with RNA from rats injected with human PTH or vehicle showed a strong association between the stimulation of monocyte chemoattractant protein-1 (MCP-1) and the anabolic effects of PTH. PTH rapidly and dramatically stimulated MCP-1 mRNA in the femora of rats receiving daily injections of PTH or in primary osteoblastic and UMR 106-01 cells. The stimulation of MCP-1 mRNA was dose-dependent and a primary response to PTH signaling via the cAMP-dependent protein kinase pathway in vitro. Studies with the mouse monocyte cell line RAW 264.7 and mouse bone marrow proved that osteoblastic MCP-1 can potently recruit osteoclast monocyte precursors and facilitate receptor activator of NF-B ligand-induced osteoclastogenesis and, in particular, enhanced fusion. Our model suggests that PTH-induced osteoblastic expression of MCP-1 is involved in recruitment and differentiation at the stage of multinucleation of osteoclast precursors. This information provides a rationale for increased osteoclast activity in the anabolic effects of PTH in addition to receptor activator of NF-B ligand stimulation to initiate greater bone remodeling. Parathyroid hormone (PTH)2 is a principal hormone regulating bone remodeling via its actions on both bone formation and bone resorption. The finding that the anabolic effect of human PTH-(1-34) on bone formation was blunted when bone resorption was inhibited indicated that active resorption is involved and enhances the in vivo anabolic effect of PTH (1-3). However, the molecular basis of the osteoclast activation in this process has not been fully studied. In order to identify the key mediators for the anabolic effects of PTH, we performed microarray using RNA from the femora of 3-month-old Sprague-Dawley female rats injected daily with hPTH-(1-34) to increase bone formation or vehicle. This was compared with rats receiving hPTH-(1-34) in a catabolic protocol by continuous infusion. PTH-(1-34) regulated numerous genes (ϳ1,000), but differentially, in both regimes (see accompanying article, Ref. 4). Notably, in the anabolic protocol, a number of cytokines and chemokines, RANKL, interleukin-6, CXCL1, and CCL2 (MCP-1), were highly induced. In contrast, none of these were significantly increased, by microarray, in the catabolic protocol. The chemokine, monocyte chemoattractant protein-1 (MCP-1, CCL2), was found to be the most highly stimulated gene from 14-day intermittent hPTH-(1-34) or hPTH-(1-31) administration (both cause over 100-fold changes). With continuous infusion of PTH, the MCP-1 mRNA was elevated less than 2-fold, and this difference indicates a potentially important role for MCP-1 in the anabolic effect of PTH.Chemokines are bioactive peptides that regulate leuk...

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Section: Discussionmentioning

confidence: 87%

Parathyroid Hormone Stimulates Osteoblastic Expression of MCP-1 to Recruit and Increase the Fusion of Pre/Osteoclasts

Li¹,

Qin²,

Bergenstock³

et al. 2007

Journal of Biological Chemistry

194

161

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“…On the other hand, cortisol can increase the expression of RANKL (receptor activator of NF-κB ligand, which enhances osteoclastogenesis) and enhance the expression of the macrophage colony-stimulating factor (MCSF). Previous studies have shown that the RANKL (Receptor Activator for Nuclear Factor-κB Ligand), MCSF (Macrophage Colony Stimulating Factor) and TGF β (Transforming Growth Factor-β) pathways played critical roles in osteoporosis (Figure 5) [15,27,28,29]. Therefore, we further elucidated whether these five secreted protein signalling pathways were implicated in bone fractures of CD.…”

Section: Resultsmentioning

confidence: 94%

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

Wang

Yang

Sheng

et al. 2016

IJMS

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Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5′-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

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“…46 However, increased csCSF-1 expression did not enhance receptor activator of nuclear factor-B (NF-B) ligand (RANKL)-driven osteoclastogenesis from marrow cells in another case. 47 Osteopetrotic (Csf1 op /Csf1 op ) mice harbor an inactivating mutation in the coding region of the CSF-1 gene and are CSF-1 deficient. [48][49][50] They are osteopetrotic due to their paucity of osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1–deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1

Zong

Sylvestre

et al. 2004

Blood

120

140

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The primary macrophage growth factor, colony-stimulating factor 1 (CSF-1), is expressed as a secreted glycoprotein or proteoglycan found in the circulation or as a biologically active cell surface glycoprotein (csCSF-1). To investigate the in vivo roles of csCSF-1, we created mice that exclusively express csCSF-1, in a normal tissue-specific and developmental manner, by transgenic expression of csCSF-1 in the CSF-1-deficient osteopetrotic (Csf1 op / Csf1 op ) background. The gross defects of Csf1 op /Csf1 op mice, including growth retardation, failure of tooth eruption, and abnormal male and female reproductive functions were corrected. Macrophage densities in perinatal liver, bladder, sublinguinal salivary gland, kidney cortex, dermis, and synovial membrane were completely restored, whereas only partial or no restoration was achieved in adult liver, adrenal gland, kidney medulla, spleen, peritoneal cavity, and intestine. Residual osteopetrosis, significantly delayed trabecular bone resorption in the subepiphyseal region of the long bone, and incomplete correction of the hematologic abnormalities in the peripheral blood, bone marrow, and spleens of CSF-1-deficient mice were also found in mice exclusively expressing csCSF-1. These data suggest that although csCSF-1 alone is able to normalize several aspects of development in IntroductionColony-stimulating factor 1 (CSF-1), also known as macrophage CSF, is the primary regulator of the mononuclear phagocyte lineage and regulates cells of the female reproductive tract. [1][2][3][4][5][6] All effects of CSF-1 are mediated by a high-affinity receptor tyrosine kinase 7-10 encoded by the c-fms proto-oncogene. 11 At least 5 mature human or mouse CSF-1 mRNAs (4.0 kb, 3.0 kb, 2.3 kb, 1.9 kb, and 1.6 kb) resulting from alternative splicing in exon 6 and the alternative usages of the 3Ј-untranslated region exons 9 and 10, [12][13][14][15][16][17][18] have been shown to encode 3 isoforms of the CSF-1 protein: a secreted glycoprotein, 19-21 a secreted proteoglycan, 22,23 and a biologically active membrane-spanning cell surface glycoprotein 18,[24][25][26][27][28][29] (for a review, see Stanley 30 ).The primary source of the circulating proteoglycan and glycoprotein CSF-1 is thought to be the endothelial cells that line the small blood vessels (for a review, see Roth and Stanley 31 ). CSF-1 is also synthesized locally, 32 for example, by osteoblasts 33,34 and by uterine epithelial cells. 3 It has been suggested that regulation at particular tissue sites is mediated by local synthesis of the membrane-spanning, cell surface CSF-1 (csCSF-1), and/or selective sequestration of the secreted proteoglycan CSF-1 (spCSF-1). 22,23,35 The csCSF-1 is encoded by a truncated mRNA in which part of the exon 6 sequence encoding the fragment containing the unique glycosaminoglycan addition site and the proteolytic cleavage sites used to release the secreted isoforms has been spliced out ( Figure 1A). 18,27 csCSF-1 is expressed in all cell types examined that express soluble CSF-1, including fib...

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Increasing membrane-bound MCSF does not enhance OPGL-driven osteoclastogenesis from marrow cells

Cited by 14 publications

References 38 publications

Parathyroid Hormone Stimulates Osteoblastic Expression of MCP-1 to Recruit and Increase the Fusion of Pre/Osteoclasts

Parathyroid Hormone Stimulates Osteoblastic Expression of MCP-1 to Recruit and Increase the Fusion of Pre/Osteoclasts

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1–deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1

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