DOI: 10.1083/jcb.148.4.665. Gelsolin Deficiency Blocks Podosome Assembly and Produces Increased Bone Mass and Strength

Gelsolin Deficiency Blocks Podosome Assembly and Produces Increased Bone Mass and Strength

10.1083/jcb.148.4.665

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Osteoclasts are unique cells that utilize podosomes instead of focal adhesions for matrix attachment and cytoskeletal remodeling during motility. We have shown that osteopontin (OP) binding to the αvβ3 integrin of osteoclast podosomes stimulated cytoskeletal reorganization and bone resorption by activating a heteromultimeric signaling complex that includes gelsolin, pp60c-src, and phosphatidylinositol 3′-kinase. Here we demonstrate that gelsolin deficiency blocks podosome assembly and αvβ3-stimulated signaling related to motility in gelsolin-null mice. Gelsolin-deficient osteoclasts were hypomotile due to retarded remodeling of the actin cytoskeleton. They failed to respond to the autocrine factor, OP, with stimulation of motility and bone resorption. Gelsolin deficiency was associated with normal skeletal development and endochondral bone growth. However, gelsolin-null mice had mildly abnormal epiphyseal structure, retained cartilage proteoglycans in metaphyseal trabeculae, and increased trabecular thickness. With age, the gelsolin-deficient mice expressed increased trabecular and cortical bone thickness producing mechanically stronger bones. These observations demonstrate the critical role of gelsolin in podosome assembly, rapid cell movements, and signal transduction through the αvβ3 integrin.

Bibliography

Chellaiah, M., Kizer, N., Silva, M., Alvarez, U., Kwiatkowski, D., & Hruska, K. A. (2000). Gelsolin Deficiency Blocks Podosome Assembly and Produces Increased Bone Mass and Strength. The Journal of Cell Biology, 148(4), 665â678.

Authors 6

Meenakshi Chellaiah (first)
Neil Kizer (additional)
Matthew Silva (additional)
Ulises Alvarez (additional)
David Kwiatkowski (additional)
Keith A. Hruska (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:45 p.m.)
Deposited	2 years, 1 month ago (July 28, 2023, 10:04 p.m.)
Indexed	1 month ago (July 25, 2025, 6:49 a.m.)
Issued	25 years, 6 months ago (Feb. 21, 2000)
Published	25 years, 6 months ago (Feb. 21, 2000)
Published Online	25 years, 6 months ago (Feb. 21, 2000)
Published Print	25 years, 6 months ago (Feb. 21, 2000)

Funders 0

None

BibTeX

@article{Chellaiah_2000, title={Gelsolin Deficiency Blocks Podosome Assembly and Produces Increased Bone Mass and Strength}, volume={148}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.148.4.665}, DOI={10.1083/jcb.148.4.665}, number={4}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Chellaiah, Meenakshi and Kizer, Neil and Silva, Matthew and Alvarez, Ulises and Kwiatkowski, David and Hruska, Keith A.}, year={2000}, month=feb, pages={665–678} }

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  "abstract": "<jats:p>Osteoclasts are unique cells that utilize podosomes instead of focal adhesions for matrix attachment and cytoskeletal remodeling during motility. We have shown that osteopontin (OP) binding to the \u03b1v\u03b23 integrin of osteoclast podosomes stimulated cytoskeletal reorganization and bone resorption by activating a heteromultimeric signaling complex that includes gelsolin, pp60c-src, and phosphatidylinositol 3\u2032-kinase. Here we demonstrate that gelsolin deficiency blocks podosome assembly and \u03b1v\u03b23-stimulated signaling related to motility in gelsolin-null mice. Gelsolin-deficient osteoclasts were hypomotile due to retarded remodeling of the actin cytoskeleton. They failed to respond to the autocrine factor, OP, with stimulation of motility and bone resorption. Gelsolin deficiency was associated with normal skeletal development and endochondral bone growth. However, gelsolin-null mice had mildly abnormal epiphyseal structure, retained cartilage proteoglycans in metaphyseal trabeculae, and increased trabecular thickness. With age, the gelsolin-deficient mice expressed increased trabecular and cortical bone thickness producing mechanically stronger bones. These observations demonstrate the critical role of gelsolin in podosome assembly, rapid cell movements, and signal transduction through the \u03b1v\u03b23 integrin.</jats:p>",
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