Cell biology of paget's disease

Reddy, Sakamuri S.V.; Menaa, Cheikh; Singer, Frederick F.R.; Demulder, Anne; Roodman, G. David

doi:10.1002/jbmr.5650140203

Cited by 54 publications

(37 citation statements)

References 24 publications

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“…Similarly, there was no difference in the number of circulating osteoclast precursors in osteoporosis patients and normal controls, but osteoclasts formed from PBMs of osteoporosis patients exhibited substantially increased resorptive activity relative to normal controls [100]. Abnormally increased osteoclast formation and activity is also a characteristic feature of Paget's disease [101]. By in vitro differentiation of PBMs into osteoclasts, it was found that PBMs from Paget's patients can give rise to a significantly higher number of osteoclasts and increased bone resorption activity than PBMs from gender-and age-matched normal controls [102].…”

Section: Using Pbms As a Working Cell Model To Study For Bone Diseasesmentioning

confidence: 92%

Circulating monocytes: an appropriate model for bone-related study

2015

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Peripheral blood monocytes (PBMs) are an important source of precursors of osteoclasts, the bone-resorbing cells and the cytokines produced by PBMs that have profound effects on osteoclast differentiation, activation, and apoptosis. So PBMs represent a highly valuable and unique working cell model for bone-related study. Finding an appropriate working cell model for clinical and (epi-)genomic studies of human skeletal disorders is a challenge. Peripheral blood monocytes (PBMs) can give rise to osteoclasts, the bone-resorbing cells. Particularly, PBMs provide the sole source of osteoclast precursors for adult peripheral skeleton where the bone marrow is normally hematopoietically inactive. PBMs can secrete potent pro- and anti-inflammatory cytokines, which are important for osteoclast differentiation, activation, and apoptosis. Reduced production of PBM cytokines represents a major mechanism for the inhibitory effects of sex hormones on osteoclastogenesis and bone resorption. Abnormalities in PBMs have been linked to various skeletal disorders/traits, strongly supporting for the biological relevance of PBMs with bone metabolism and disorders. Here, we briefly review the origin and further differentiation of PBMs. In particular, we discuss the close relationship between PBMs and osteoclasts, and highlight the utility of PBMs in study the pathophysiological mechanisms underlying various skeletal disorders.

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Section: Using Pbms As a Working Cell Model To Study For Bone Diseasesmentioning

confidence: 92%

Circulating monocytes: an appropriate model for bone-related study

2015

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“…16,17) In particular, irregularity of the geometry of osteoclast resorption cavities has been demonstrated in Paget s disease 17) and glucocorticoid-induced osteoporosis. 19) Since these skeletal disorders display an increased resorption activity which is attributable to alterations in osteoclast biology, 20,21) insights into the association of osteoclast biology, geometry of osteoclastic resorption cavities, and microstructure of newly formed bone should be helpful to understand the mechanisms responsible for the maintenance of bone quality in biological systems.…”

Section: Introductionmentioning

confidence: 99%

Disruption of Collagen Matrix Alignment in Osteolytic Bone Metastasis Induced by Breast Cancer

2016

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Breast cancer is highly metastatic to bone tissue and causes osteolytic lesions through osteoclast activation. Although the effects of osteolytic metastasis on bone quantity have been well studied, whether osteoclast activation induced by cancer bone metastasis affects the bone microstructure, a notable aspect of the bone quality, remains uncertain. The aim of this study was to clarify the effect of osteolytic bone metastasis in breast cancer on the microstructure of the bone matrix, particularly the integrity of collagen bril orientation. Osteolytic breast cancer cells induced hyperactivation of osteoclasts both in vivo and in vitro. Osteoclasts differentiated by culture of monocytes in the cancer cell-derived conditioned medium had an increased number of nuclei; more speci c podosome structures were organized compared to osteoclasts differentiated in the control medium. These observations suggest that the resorptive capacity of a single osteoclast was abnormally upregulated in the cancer-involving environment, causing geometrically irregular resorption cavities. Histological studies on mouse femurs with metastasis of breast cancer MDA-MB-231 cells revealed that the osteoclasts in the metastatic bone were abnormally large and they generated resorption cavities that are irregular both in size and in shape. Notably, collagen matrix in newly formed bone in metastatic bone exhibited a signi cantly disorganized architecture. To the best of our knowledge, this is the rst report demonstrating that osteolytic bone metastasis induces the disruption of bone matrix alignment, which determines the mechanical function of bone in both intact and diseased bone tissue.

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“…Paget's disease is characterized by uncontrolled bone remodeling due to increased bone resorption by osteoclasts (97). A hyperosteoclastogenic bone marrow microenvironment due to abnormal production of or response to cytokines (IL-6) and hormones [1,25(OH) 2 D 3 ], perhaps triggered by the presence of paramyxoviral-like nuclear inclusions, has been suggested as a potential mechanism (97). Only recently, enhanced RANKL expression was observed in a bone marrow stromal cell line developed from a patient with Paget's disease (98).…”

Section: Drug-induced Osteoporosismentioning

confidence: 99%

The Role of Receptor Activator of Nuclear Factor-κB Ligand and Osteoprotegerin in the Pathogenesis and Treatment of Metabolic Bone Diseases¹

Hofbauer

Heufelder

2000

The Journal of Clinical Endocrinology & Metabolism

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BONE IS permanently turned over by the balanced and coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts, resulting in continuous renewal, functional response to external and internal stimuli, and structural integrity (1-3). Inappropriate bone resorption caused by enhanced osteoclast formation and activity has been previously implicated in the pathogenesis of many metabolic bone diseases. Strategies to inhibit bone resorption have emerged as potent and promising tools for the prevention and treatment of bone and mineral disorders (1-3). The recent discovery and characterization of a novel cytokine system, the tumor necrosis factor (TNF) ligand family member, receptor activator of nuclear factor-B ligand (RANKL/ OPGL/ODF/TRANCE) (4 -7); 1 its receptor, receptor activator of nuclear factor B (RANK/ODAR) (7); and its soluble (decoy) receptor, osteoprotegerin (OPG/OCIF/TR1) (8 -11), has established a novel paradigm of osteoclast biology: RANKL, RANK, and OPG constitute the three essential regulatory components of osteoclast formation, fusion, survival, activation, and apoptosis (12)(13)(14). This article 2 reviews the molecular aspects of this novel cytokine system and its regulation and modulation by various osteotropic agents. Moreover, we summarize the implications of this cytokine system on the pathogenesis of various bone diseases and discuss the therapeutic potential of OPG in the clinical setting. RANKL/OPGL/ODF/TRANCE: the ligandThe TNF ligand family member, osteoprotegerin ligand (OPGL)/osteoclast differentiation factor (ODF) was discovered in 1998 by two groups (4, 5) as the cognate ligand for OPG/ osteoclastogenesis inhibitory factor (OCIF) (8, 9). This factor had been identified by the same two groups the year before and was shown to be identical to TNF-related activation-induced cytokine (TRANCE) (6) and receptor activator of nuclear factor-B ligand (RANKL) (7). RANKL will be the preferred term according to a consensus nomenclature (12). RANKL is a cellbound polypeptide of 317 amino acids (4, 5) that is cleaved by a protease, TNF␣-converting enzyme-like protease (TACE) (15), at position 140 or 145, respectively, to give rise to a shorter soluble ectodomain variant of similar activity (4, 15).The major sources of RANKL production in the bone/bone marrow microenvironment are bone marrow stromal cells, osteoblasts, chondrocytes, mesenchymal cells of the periosteum, osteoclasts, endothelial cells, and T cells (4 -7, 16). Detailed analyses of its extraskeletal tissue distribution revealed RANKL messenger ribonucleic acid (mRNA) and protein production in brain, heart, kidney, skeletal muscle, and skin (16). Of note, RANKL production is highest in undifferentiated stromal cells and is greatly reduced once these multipotential mesenchymal cells become terminally committed to the osteoblastic phenotype (17-19). Interestingly, the RANKL gene promoter structure contains both vitamin D and glucocorticoid response elements as well as a binding site for the essential osteoblastic transcriptio...

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Cell biology of paget's disease

Cited by 54 publications

References 24 publications

Circulating monocytes: an appropriate model for bone-related study

Circulating monocytes: an appropriate model for bone-related study

Disruption of Collagen Matrix Alignment in Osteolytic Bone Metastasis Induced by Breast Cancer

The Role of Receptor Activator of Nuclear Factor-κB Ligand and Osteoprotegerin in the Pathogenesis and Treatment of Metabolic Bone Diseases¹

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Cell biology of paget's disease

Cited by 54 publications

References 24 publications

Circulating monocytes: an appropriate model for bone-related study

Circulating monocytes: an appropriate model for bone-related study

Disruption of Collagen Matrix Alignment in Osteolytic Bone Metastasis Induced by Breast Cancer

The Role of Receptor Activator of Nuclear Factor-κB Ligand and Osteoprotegerin in the Pathogenesis and Treatment of Metabolic Bone Diseases1

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The Role of Receptor Activator of Nuclear Factor-κB Ligand and Osteoprotegerin in the Pathogenesis and Treatment of Metabolic Bone Diseases¹