Osteoclastic bone resorption: In vitro analysis of the rate of resorption and migration of individual osteoclasts

Kanehisa, Junya; Heersche, J. N. M.

doi:10.1016/8756-3282(88)90106-8

Cited by 144 publications

(86 citation statements)

References 12 publications

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“…By measuring the rate of migration and bone resorption of osteoclasts using time-lapse recording and scanning electron microscopy, they found that osteoclasts resorb bone matrix at rates up to 400 m 3 /h and migrate across the surface of bone slices up to 100 m/h. Thus, the reorganization of the cytoarchitecture of osteoclasts must be fast, a requirement in keeping with the ability of podosomes to disappear, form, and reorganize in minutes (12). We demonstrate here that stress fiber formation/podosome disassembly and stress fiber disassembly and podosomes assembly represent the sequence of events observed in Rho Val-14-transduced cells.…”

Section: Effects Of Rho Transduction On Osteoclast Migration and Bonementioning

confidence: 84%

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Rho-A Is Critical for Osteoclast Podosome Organization, Motility, and Bone Resorption

Chellaiah

Soga

Swanson

et al. 2000

Journal of Biological Chemistry

243

230

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Rho plays a regulatory role in the formation of actin stress fibers and focal adhesions, and it is also involved in integrin-mediated signaling events. To study the role of Rho in ␣ v ␤ 3 /gelsolin-dependent signaling, the HIV-Tat peptide, hemagglutinin (HA)-tagged Rho Val-14 (constitutively active) and Rho Asn-19 (dominant negative) were transduced into avian osteoclasts. Protein transduction by HA-Tat was highly efficient, and 90 -100% of the cells were transduced with HA-tagged proteins. We demonstrate here that Rho Val-14 transduction (100 nM) stimulated gelsolin-associated phosphatidylinositol 3-kinase activity, podosome assembly, stress fiber formation, osteoclast motility, and bone resorption, mimicking osteoclast stimulation by osteopontin/␣ v ␤ 3. The effects of Rho Val-14 transduction stimulation was time-dependent. C3 exoenzyme blocked the effects of RhoVal-14 and induced podosome disassembly, loss of motility, and inhibition of bone resorption. Transduction of Rho Asn-19 produced podosome disassembly, and blocked osteopontin stimulation. These data demonstrate that integrin-dependent activation of phosphoinositide synthesis, actin stress fiber formation, podosome reorganization for osteoclast motility, and bone resorption require Rho stimulation.

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Section: Effects Of Rho Transduction On Osteoclast Migration and Bonementioning

confidence: 84%

“…The C3 enzyme also inhibits bone resorption (9). Osteoclasts are highly motile cells, which depend on rapid changes in their actin cytoskeleton to accomplish their ordered cycles of movement and attachment during bone resorption (11)(12)(13)(14). However, osteoclasts do not have the focal adhesion attachment structures characteristic of other cells (15).…”

mentioning

confidence: 99%

Rho-A Is Critical for Osteoclast Podosome Organization, Motility, and Bone Resorption

Chellaiah

Soga

Swanson

et al. 2000

Journal of Biological Chemistry

243

230

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“…Ruffled borders and sealing zones are seen only in non-motile osteoclasts during the resorption phase and subsequently disappear during the course of osteoclast migration (Kanehisa & Heersche 1988). Osteoclast interaction with extracellular matrix (ECM) plays a key role in the migratory and resorptive phases of the osteoclast cycle and a substantial body of evidence suggests that integrin receptors play a key role in the osteoclast resorption process (Horton & Rodan 1996).…”

Section: Introductionmentioning

confidence: 99%

“…Osteoclasts actively migrate on bone surfaces and undergo alternating cycles of migration and resorption (Kanehisa & Heersche 1988. Ruffled borders and sealing zones are seen only in non-motile osteoclasts during the resorption phase and subsequently disappear during the course of osteoclast migration (Kanehisa & Heersche 1988).…”

Section: Introductionmentioning

confidence: 99%

Peptidomimetic antagonists of alphavbeta3 inhibit bone resorption by inhibiting osteoclast bone resorptive activity, not osteoclast adhesion to bone

Carron

Meyer

Engleman

et al. 2000

Journal of Endocrinology

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Osteoclasts are actively motile on bone surfaces and undergo alternating cycles of migration and resorption. Osteoclast interaction with the extracellular matrix plays a key role in the osteoclast resorptive process and a substantial body of evidence suggests that integrin receptors are important in osteoclast function. These integrin receptors bind to the Arg-Gly-Asp (RGD) sequence found in a variety of extracellular matrix proteins and it is well established that the interaction of osteoclast v 3 integrin with the RGD motif within bone matrix proteins is important in osteoclast-mediated bone resorption. In this study, we characterized the effects of two synthetic peptidomimetic antagonists of v 3, SC-56631 and SC-65811, on rabbit osteoclast adhesion to purified matrix proteins and bone, and on bone resorption in vitro. SC-56631 and SC-65811 are potent inhibitors of vitronectin binding to purified v 3. Both SC-56631 and SC-65811 inhibited osteoclast adhesion to osteopontinand vitronectin-coated surfaces and time-lapse video microscopy showed that osteoclasts rapidly retract from osteopontin-coated surfaces when exposed to SC-56631 and SC-65811. SC-56631 and SC-65811 blocked osteoclast-mediated bone resorption in a dose-responsive manner. Further analysis showed that SC-65811 and SC-56631 reduced the number of resorption pits produced per osteoclast and the average pit size. SC-65811 was a more potent inhibitor of bone resorption and the combination of reduced pit number and size led to a 90% inhibition of bone resorption. Surprisingly, however, osteoclasts treated with SC-65811, SC-56631 or the disintegrin echistatin, at concentrations that inhibit bone resorption did not inhibit osteoclast adhesion to bone. These results suggest that v 3 antagonists inhibited bone resorption by decreasing osteoclast bone resorptive activity or efficiency but not by inhibiting osteoclast adhesion to bone per se.

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“…Adhesion structures called podosomes present in highly motile cells are also found in osteoclasts. Osteoclasts are unique, because they use the speed of podosome assembly and disassembly to generate high rates of motility (13,14). Bone resorption involves active motility of osteoclasts on bone surfaces to be resorbed.…”

mentioning

confidence: 99%

Rho-dependent Rho Kinase Activation Increases CD44 Surface Expression and Bone Resorption in Osteoclasts

Chellaiah

Biswas

Rittling

et al. 2003

Journal of Biological Chemistry

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Osteoclasts from osteopontin-efficient mice exhibit decreased CD44 surface expression. Osteopontin (OPN)/ ␣ v ␤ 3 generated Rho signaling pathway is required for the surface expression of CD44. In this work we show the Rho effector, Rho kinase (ROK-␣), to be a potent activator of CD44 surface expression. ROK-␣ activation was associated with autophosphorylation, leading to its translocation to the plasma membrane, as well as its association with CD44. ROK-␣ promoted CD44 surface expression through phosphorylation of CD44 and ezrinradixin-moesin (ERM) proteins and CD44⅐ERM⅐actin complex formation. Osteoclasts from OPN؊/؊ mice exhibited an ϳ55-60% decrease in basal level ROK-␣ phosphorylation as compared with wild type osteoclasts. Furthermore, RhoVal-14 transduction was only partially effective in stimulating ROK-␣/CD44 phosphorylation, as well as CD44 surface expression, in these osteoclasts. Studies on the inhibition of Rho by C3 transferase or ROK-␣ by the specific inhibitor, Y-27632, showed a decrease in the phosphorylation mediated by ROK-␣ and CD44 surface expression. Neutralizing antibodies to ␣ v , ␤ 3 , or CD44 inhibited the migration and bone resorption of wild type osteoclasts. However, only anti-␣ v or -␤ 3 antibodies blocked OPN-induced phosphorylation of ROK-␣, CD44, and the ERM proteins. Our results strongly suggest a role for ROK-␣ in ␣ v ␤ 3 -mediated Rho signaling, which is required for the phosphorylation events and CD44 surface expression. The functional deficiencies in the Rho effector(s) because of the lack of OPN were associated with decreased CD44 surface expression and hypomotility in the OPN؊/؊ osteoclasts. Finally, we find that cooperativity exists between ␣ v ␤ 3 and CD44 for osteoclast motility and bone resorption.Osteopontin (OPN), 1 a major component of protein complexes organized around mineralization foci, is a phosphorylated acidic glycoprotein synthesized by many cell types throughout the body in response to stress or injury (1-3). Although osteopontin serves many functions in bone cells besides regulating mineralization of the matrix, regulation of osteoclast motility and resorption is perhaps its most important. Osteopontin is a ligand for several cell surface adhesion receptors, such as, and ␣ 9 ␤ 1 (reviewed in Refs. 4 and 5). The hyaluronic acid receptor, CD44, is also a receptor for OPN (6). CD44 has been implicated in chemotaxis mediated by OPN (6, 7), as well as in bone resorption (8). CD44 expression was reported in osteoclasts of human and rat bone sections (9 -11). Weber et al. (6), have shown that the binding of soluble OPN to fibroblasts transfected with CD44 cDNA is blocked by anti-CD44 antibody. Moreover, anti-CD44 or anti-OPN antibodies inhibited the migration of CD44-transfected fibroblasts toward OPN in Boyden chambers (7), suggesting CD44-OPN interaction and a role in chemotactic function. Expression of OPN and CD44 was increased in migrating fetal fibroblasts (12), and the colocalization of CD44 and OPN was prominent at the leading edge of migrating osteoclast...

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Osteoclastic bone resorption: In vitro analysis of the rate of resorption and migration of individual osteoclasts

Cited by 144 publications

References 12 publications

Rho-A Is Critical for Osteoclast Podosome Organization, Motility, and Bone Resorption

Rho-A Is Critical for Osteoclast Podosome Organization, Motility, and Bone Resorption

Peptidomimetic antagonists of alphavbeta3 inhibit bone resorption by inhibiting osteoclast bone resorptive activity, not osteoclast adhesion to bone

Rho-dependent Rho Kinase Activation Increases CD44 Surface Expression and Bone Resorption in Osteoclasts

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