Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesis

Leung, Roland; Wang, Yongqiang; Cuddy, Karl; Sun, Cong; Magalhaes, Joyce; Grynpas, Marc D.; Glogauer, Michael

doi:10.1359/jbmr.091114

Cited by 68 publications

(70 citation statements)

References 51 publications

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“…The fusion first occurs to a portion of the filopodia. Previous reports have shown that FLNA, Rac1, and Rac2 are related to the OC chemotaxis during differentiation (Wang et al, 2008;Leung et al, 2010;Itokowa et al, 2011;Sun et al, 2013). FLNA allows Rho GTPases to accumulate at the front of filopodia, and a cascade amplifies the effect to Rho GTPases (Nobes and Hall, 1995;Ohta et al, 2006;Leung et al, 2010).…”

Section: Oc Fusion Processmentioning

confidence: 98%

“…FLNA is an actin-bound protein that forms a larger network with F-actin through cross-linking interactions (Stossel et al, 2001;Popowicz et al, 2006;Leung et al, 2010). The Rho GTPases are largely concentrated in the filopodia and function in cascade amplification by FLNA (Leung et al, 2010).…”

Section: Oc Differentiation and Expression Of Specific Enzymesmentioning

confidence: 99%

“…The Rho GTPases are largely concentrated in the filopodia and function in cascade amplification by FLNA (Leung et al, 2010). Most Rho GTPases and FLNA showed reduced expression on the first day of induction, indicating a decline in cytoskeleton stability.…”

Section: Oc Differentiation and Expression Of Specific Enzymesmentioning

confidence: 99%

“…Cell fusion and migration are crucial for OC differentiation and maturation (Leung et al, 2010;Miyamoto, 2011). Remarkably, there is only 1 type of filopodium present in undifferentiated cells.…”

Section: Changes and Adjustment Of Filopodiamentioning

confidence: 99%

“…Previous studies primarily focused on Rho GTPase-controlled cell migration of monocytes through filopodium regulation, thus influencing fusion (Leung et al, 2010;Zhao et al, 2010;Xing et al, 2012) and manipulating the formation of the sealing zone by regulating podosome distribution, which in turn affects bone resorption (Chellaiah, 2005;Jurdic et al, 2006;Itzstein et al, 2011). However, little is known regarding the other roles of filopodia and podosomes in OC differentiation and cell fusion.…”

Section: Introductionmentioning

confidence: 99%

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New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts

et al. 2014

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ABSTRACT. The cytoskeleton mediates various cellular processes such as differentiation and fusion, including in the filopodia and podosomes. However, apart from cell migration and formation of the sealing zone, little is known regarding the changes and related regulatory mechanisms of the cytoskeleton and additional roles of the filopodia and podosomes during the differentiation and fusion of osteoclasts. The cytomorphology and cytoskeleton of osteoclasts in the differentiation process were evaluated using tartrate-resistant acid phosphatase staining and immunofluorescence staining. Moreover, the expression levels of Rho GTPases and enzymes related to osteoclast differentiation and bone resorption were detected by quantitative reverse transcription-polymerase chain reaction. We detected 3 types of filopodia in osteoclast precursors and only 1 type of filopodia in undifferentiated cells. Mature osteoclasts were completely devoid of filopodia. Interestingly, cell fusion was highly specific, and the fusion New roles of filopodia and podosomes of osteoclasts initially occurred to the filopodia. Confocal images revealed that F-actin and microtubules significantly differed among fused cells. These results suggest that filopodia and podosomes not only play important roles in cell migration and the formation of sealing zones but also in the prefusion selectivity of 2 cells and the movement direction of the cell nucleus and cytoplasm during the fusion process. In addition, cdc42v1, RhoU, and RhoF regulate the formation of 3 types of filopodia during various stages of differentiation, while Rac1, Rac2, and filament A may be associated with cell selectivity during the fusion process.

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Section: Oc Fusion Processmentioning

confidence: 98%

Section: Oc Differentiation and Expression Of Specific Enzymesmentioning

confidence: 99%

Section: Oc Differentiation and Expression Of Specific Enzymesmentioning

confidence: 99%

Section: Changes and Adjustment Of Filopodiamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts

et al. 2014

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Comparative proteomics analysis of microvesicles in human serum for the evaluation of osteoporosis

Huo

Qiao

et al. 2019

Electrophoresis

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Osteoporosis is an emerging health issue worldwide. Due to the decrease of bone mineral density and the deterioration of skeletal microarchitecture, osteoporosis could lead to increased bone fragility and higher fracture risk. Since lack of specific symptoms, novel serum proteomic indicators are urgently needed for the evaluation of osteoporosis. Microvesicles (MVs) are important messengers widely present in body fluids and have emerged as novel targets for the diagnosis of multiple diseases. In this study, MVs were successfully isolated from human serum and comprehensively characterized. Comparative proteomics analysis revealed differential MVs protein profiling in normal subjects, osteopenia patients, and osteoporosis patients. In total, about 200 proteins were identified and quantified from serum MVs, among which 19 proteins were upregulated (fold change >2) and five proteins were downregulated (fold change <0.5) in osteopenia group and osteoporosis group when compared with the normal group. Three protein candidates were selected for initial verification, including Vinculin, Filamin A, and Profilin 1. Profilin 1 was further pre‐validated in an independent sample set, which could differentiate osteoporosis group from osteopenia group and normal group (p < 0.05). Our data collectively demonstrate that serum MVs proteome can be valuable indicators for the evaluation and diagnostics of bone loss disease.

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Recent advances in understanding the mechanisms of osteoclast precursor fusion

Oursler

2010

J of Cellular Biochemistry

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Bone marrow macrophages fuse on the bone surface to form multinucleated osteoclasts that then organize to efficiently resorb bone. Many, if not all, of the stages of macrophage fusion involve cytoskeletal components that reorganize the cells. Recruitment may involve chemotactic responses to bone matrix protein and calcium ion gradients and/or chemokine production by bone forming osteoblasts. The roles of integrins vary, depending on the particular subunits with some interfering with fusion and others having a participatory role. RANKL is essential for fusion and many identified modulators of fusion influence RANKL signaling pathways. Tetraspanins have been implicated in fusion of macrophages and myoblasts, but differences in impacts exist between these two cell types. Macrophage recruitment to apoptotic cells prior to their engulfment is driven by the exposed phospholipids on the external surface of the apoptotic cells and there is evidence that this same identification mechanism is employed in macrophage fusion. Because loss of cadherin or ADAM family members suppresses macrophage fusion, a crucial role for these membrane glycoproteins is evident. The Ig membrane glycoprotein superfamily members CD200 and MFR/ SIRPα are involved in macrophage fusion, although their influences are unresolved. Differential screenings have identified the structurally related membrane proteins DC-STAMP and OC-STAMP as required components for fusion and the contributions to fusion remain active areas of investigation. While many of the key components involved in these processes have been identified, a great deal of work remains in resolving the precise processes involved and the interactions between key contributors to multinucleated osteoclast formation.

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Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesis

Cited by 68 publications

References 51 publications

New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts

New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts

Comparative proteomics analysis of microvesicles in human serum for the evaluation of osteoporosis

Recent advances in understanding the mechanisms of osteoclast precursor fusion

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