The F-actin modulator SWAP-70 controls podosome patterning in osteoclasts

Roscher, Anne; Hasegawa, Tomoka; Dohnke, Sebastian; Ocaña-Morgner, Carlos; Amizuka, Norio; Jessberger, Rolf; Garbe, Annette I.

doi:10.1016/j.bonr.2016.07.002

Cited by 22 publications

(18 citation statements)

References 40 publications

(54 reference statements)

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“…Osteoclast‐induced bone resorption is mediated by an adhesion structure called the sealing zone, which is formed by fusion of podosomes (24, 25). To understand the effect of REV‐ERB agonism on podosome patterning and assembly, we analyzed the ratio of 3 patterns of podosome organization, including podosome clusters, actin rings, and podosome belts (26). Podosomes consisting of a central actin core and a surrounding ring of adhesion molecules such as vinculin were analyzed by using a confocal microscope.…”

Section: Resultsmentioning

confidence: 99%

REV‐ERB agonism suppresses osteoclastogenesis and prevents ovariectomy‐induced bone loss partially via FABP4 upregulation

et al. 2018

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REV-ERBs (REV-ERBα and REV-ERBβ) are transcription repressors and circadian regulators. Previous investigations have shown that REV-ERBs repress the expression of target genes, including MMP9 and CX3CR1, in macrophages. Because MMP9 and CX3CR1 reportedly participate in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, we inferred that REV-ERBs might play a role in osteoclastogenesis. In the present study, we found that the REV-ERBα level decreased significantly during RANKL-induced osteoclast differentiation from primary bone marrow-derived macrophages (BMMs). REV-ERBα knockdown by small interfering RNA in BMMs resulted in the enhanced formation of osteoclasts, whereas REV-ERBβ knockdown showed no effect on osteoclast differentiation. Moreover, the REV-ERB agonist SR9009 inhibited osteoclast differentiation and bone resorption. Intraperitoneal SR9009 administration prevented ovariectomy-induced bone loss; this effect was accompanied by decreased serum RANKL and C-terminal telopeptide of type I collagen levels and increased osteoprotegerin levels. Further investigation revealed that NF-κB and MAPK activation and nuclear factor of activated T cells, cytoplasmic 1, and c-fos expression were suppressed by SR9009. The level of reactive oxygen species was also decreased by SR9009, with NADPH oxidase subunits also being down-regulated. In addition, an expression microarray showed that FABP4, an intracellular lipid-binding protein, was up-regulated by REV-ERB agonism. BMS309403, an inhibitor of FABP4, partially prevented the suppression of osteoclastogenesis by SR9009 through stabilizing phosphorylation of p65. To summarize, our results proved that the REV-ERB agonism inhibited osteoclastogenesis partially via FABP4 up-regulation.-Song, C., Tan, P., Zhang, Z., Wu, W., Dong, Y., Zhao, L., Liu, H., Guan, H., Li, F. REV-ERB agonism suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss partially via FABP4 upregulation.

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Section: Resultsmentioning

confidence: 99%

REV‐ERB agonism suppresses osteoclastogenesis and prevents ovariectomy‐induced bone loss partially via FABP4 upregulation

et al. 2018

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“…Therefore, for a SZ ring to be active in osteoclastic resorption, a sufficient degree of cooperativity is required, via topographic stabilization or other cues. Such cues can include, for example, the switch associated with the protein SWAP-70, which is required for efficient resorption and which reduced expression results in osteopetrosis [59,60]. The adhesive response to bone is determined by both local and global aspects interweaved.…”

Section: Discussionmentioning

confidence: 99%

Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

Shemesh

Addadi

Geiger

2017

J. R. Soc. Interface.

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Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. It is commonly assumed that the structure and dynamic properties of the SZ depend on the physical and chemical properties of the substrate. Considering the unique complex structure of native bone, elucidation of the relevant parameters affecting SZ formation and stability is challenging. In this study, we examined in detail the dynamic response of the SZ to the microtopography of devitalized bone surfaces, taken from the same area in cattle femur. We show that there is a significant enrichment in large and stable SZs (diameter larger than 14 mm; lifespan of hours) in cells cultured on rough bone surfaces, compared with small and fast turning over SZ rings (diameter below 7 mm; lifespan approx. 7 min) formed on smooth bone surfaces. Based on these results, we propose that the surface roughness of the physiologically relevant substrate of osteoclasts, namely bone, affects primarily the local stability of growing SZs.

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“…However, at the late stage of osteoclastogenesis, osteoclastic polarization characterized the final maturation of bone resorptive osteoclasts. Notably, during the bone resorption process, osteoclastic polarization involves rearrangement of the actin cytoskeleton, in which a filamentous (F)-actin ring that comprises dense continuous zones of highly dynamic podosomes are formed and consequently an area of membrane that develops into the ruffled border is isolated [5,6].…”

Section: Introductionmentioning

confidence: 99%

The role of Rho GTPases’ substrates Rac and Cdc42 in osteoclastogenesis and relevant natural medicinal products study

et al. 2020

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Recently, Rho GTPases substrates include Rac (Rac1 and Rac2) and Cdc42 that have been reported to exert multiple cellular functions in osteoclasts, the most prominent of which includes regulating the dynamic actin cytoskeleton rearrangements. In addition, natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Although currently, there are reports about the natural product, which could play a therapeutic role in bone loss diseases (osteoporosis and osteolysis) through the regulation of Rac1/2 and Cdc42 during osteoclasts cytoskeletal structuring. There have been several excellent studies for exploring the therapeutic potentials of various natural products for their role in inhibiting cancer cells migration and function via regulating the Rac1/2 and Cdc42. Herein in this review, we try to focus on recent advancement studies for extensively understanding the role of Rho GTPases substrates Rac1, Rac2 and Cdc42 in osteoclastogenesis, as well as therapeutic potentials of natural medicinal products for their properties on the regulation of Rac1, and/or Rac2 and Cdc42, which is in order to inspire drug discovery in regulating osteoclastogenesis.

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The F-actin modulator SWAP-70 controls podosome patterning in osteoclasts

Cited by 22 publications

References 40 publications

REV‐ERB agonism suppresses osteoclastogenesis and prevents ovariectomy‐induced bone loss partially via FABP4 upregulation

REV‐ERB agonism suppresses osteoclastogenesis and prevents ovariectomy‐induced bone loss partially via FABP4 upregulation

Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

The role of Rho GTPases’ substrates Rac and Cdc42 in osteoclastogenesis and relevant natural medicinal products study

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