Recent advances in the ultrastructural assessment of osteoclastic resorptive functions

Sasaki, Takahísa

doi:10.1002/(sici)1097-0029(19960201)33:2<182::aid-jemt8>3.0.co;2-v

Cited by 24 publications

(17 citation statements)

References 29 publications

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“…Namely, by means of postembedding immunogold technique, H ϩ -ATPase was localized in the RER cisterns, Golgi apparatus, pale vacuoles, and ruffled border membranes (Sasaki et al, 1994;Sasaki, 1996;Sahara and Sasaki, 2001). In the present study, bafilomycin A1 treatment altered such subcellular localization of H ϩ -ATPase molecules in osteoclasts.…”

Section: Discussionsupporting

confidence: 48%

“…The involvement of vacuolar-type H ϩ -ATPase in osteoclastic bone resorption is supported by evidence that the macrolide antibiotic, bafilomycin A1, reduced proton transport in isolated medullary bone-derived microsomes containing H ϩ -ATPase and dose-dependently inhibited osteoclastic bone resorption in vitro (Bowman et al, 1988;Sundquist et al, 1990;Sasaki et al, 1994;Sasaki, 1996). Concerning the effects of bafilomycin A1 on osteoclastic resorption, Okahashi et al (1997) reported that both bafilomycin A1 and concanamycin B induced apoptotic cell death in cultured osteoclasts at 1-2 ϫ 10 Ϫ4 M, which is much higher than the concentrations we used (10 Ϫ10 ϳ10 Ϫ8 M).…”

Section: Discussionmentioning

confidence: 95%

“…Solubilization of hydroxyapatite crystals results in exposure of the type 1 collagen of the bone matrix. Resorption lacunae are then formed by collagen degradation, mediated mainly by lysosomal cysteine proteinases such as cathepsins, which are highly and selectively expressed in osteoclasts (Sasaki, 1996;Littlewood-Evans et al, 1997;Kamiya et al, 1998;Yamaza et al, 1998;Sahara and Sasaki, 2001). To evaluate the specific biological functions of these enzymes, it is necessary to examine the effects of specific and potent inhibitors on the ultrastructure and functions of osteoclasts in vitro.…”

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Specific biological functions of vacuolar‐type H⁺‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

et al. 2003

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We report the effects of specific and potent inhibitors of vacular-type H ϩ -ATPase and lysosomal cysteine proteinases, cathepsins, on the ultrastructure, expression of these enzymes, and resorptive functions of cultured osteoclasts. Osteoclasts were formed by co-culture of marrow cells and calvarial primary osteoblasts of ddY mice. Formed osteoclasts were cultured on dentine slices for 6 -48 hr with either an H ϩ -ATPase inhibitor, bafilomycin A1, or a cysteine proteinase inhibitor, E-64. In control cultures with no additive, osteoclasts were structurally characterized by the development of ruffled borders and clear zones, and formed many resorption lacunae on dentine slices. Both H ϩ -ATPase and cathepsin K were strongly expressed in the ruffled borders of these osteoclasts. In bafilomycin A1-treated cultures, osteoclasts lacked ruffled borders, and resorption lacuna formation was markedly diminished. This effect of bafilomycin A1 on osteoclast structure was reversible by removal of the compound. Bafilomycin A1 treatment altered the subcellular localization and decreased the expression of H ϩ -ATPase molecules. H ϩ -ATPase expression was observed throughout the cytoplasm, but not along the plasma membranes facing dentine slices. On the other hand, E-64 treatment did not affect the ultrastructure of osteoclasts and the expression of enzyme molecules. Although E-64 showed no effect on demineralization of dentine slices, it dose-dependently reduced resorption lacuna formation. Our results suggest that 1) bafilomycin A1 dose-dependently inhibits resorption lacuna formation via inhibition of ruffled border formation, 2) H ϩ -ATPase expression is closely associated with the cytoskeleton of osteoclasts, and 3) E-64 treatment decreases the depth of resorption lacunae, by inhibition of secreted cathepsin K activity, but does not impair ruffled border formation and the associated expression of H ϩ -ATPase and cathepsin K in osteoclasts. Anat Rec Part A 270A: 152-161, 2003.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 95%

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confidence: 99%

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Specific biological functions of vacuolar‐type H⁺‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

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“…This paper first reports the effects of EMD on oste- oclasts, the principal cells directly responsible for solubilization of hydroxyapatite crystals and the subsequent degradation of insoluble type-1 collagen of bone matrix (see reviews by Delaisse and Vaes, 1992;Sasaki, 1996). Degradation of bone type-I collagen during resorption lacuna formation is mediated mainly by cathepsin K, a lysosomal cysteine proteinase, highly and selectively expressed in osteoclasts (Kamiya et al, 1998;LittlewoodEvans et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Porcine enamel matrix derivative enhances trabecular bone regeneration during wound healing of injured rat femur

et al. 2001

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To elucidate the effects of enamel matrix derivative (EMD: Emdogain) on bone regeneration in rat femurs after drill-hole injury, defects in bone were filled with either EMD or its carrier, PGA, as control. On postoperative days 4 to 28, dissected femurs were examined by means of various morphological approaches. In both experimental groups, formation of trabecular bone, which was immunostained for bone sialoproteins (BSP), had occurred in the medullary cavities at cylindrical bone defects on Day 7 postoperatively. Cuboidal osteoblasts were clearly observed on these newly-formed BSP-positive bone trabeculae. On Days 7 and 14, many multinucleated giant cells, which strongly expressed cathepsin K, had appeared on these bone trabeculae, indicating active bone remodeling. In these bone trabeculae, Ca and P weight % and Ca/P ratio were similar to those of cortical bone, and there was no significant difference between the PGA-and EMD-applied groups. Bone volume fraction of newly-formed bone trabeculae on Day 7 postoperatively was significantly higher in the EMD-applied group than in the PGA-applied controls. Because of active bone remodeling and the marked decrease of bone volume, on Days 14 and 28 postoperatively, however, there was no longer a significant difference in trabecular bone volume fraction between the experimental groups. Our results suggest that EMD possesses an osteo-promotive effect on bone and medullary regeneration during wound healing of injured long bones. Anat Rec 264: 438 -446, 2001.

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“…In bone resorption, osteoclasts are the principal cells directly responsible for solubilization of mineral components (i.e., calcium hydroxyapatite) and the subsequent degradation of insoluble type-1 collagen of the bone matrix and are characterized structurally by a prominent ruffled border-clear zone complex facing the resorptive bone surfaces (see reviews by Vaes, 1988;Delaisse and Vaes, 1992;Sasaki, 1996). In the initial phase of osteoclastic bone resorption, hydroxyapatite crystals are decalcified by acidification of the subosteoclastic microenvironment created by vacuolar-type H ϩ -ATPase, which is highly localized in the ruffled border membranes of osteoclasts (Baron et al, 1985;Vaes, 1988;Sundquist et al, 1990;Vaananen et al, 1990;Sasaki et al, 1994;Yokoya et al, 1997).…”

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Immunolocalization of vacuolar‐type H⁺‐ATPase, cathepsin K, matrix metalloproteinase‐9, and receptor activator of NFkB ligand in odontoclasts during physiological root resorption of human deciduous teeth

et al. 2001

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To investigate the cellular mechanisms of physiological root resorption in human deciduous teeth, the authors examined the immunocytochemical localization of vacuolar-type H ϩ -ATPase, a lysosomal cysteine proteinase, cathepsin K, matrix metalloproteinase-9 (MMP-9), and receptor activator of NFKB ligand (RANKL) in odontoclasts. H ϩ -ATPase, cathepsin K, and MMP-9 are the most important enzymes for decalcification of apatite crystals and degradation of type-I collagen. In addition, RANKL is one of the key regulatory molecules in osteoclast formation and functions. Odontoclasts developed extensive ruffled borders and clear zones apposed to the resorbing root dentine surfaces. On immunoelectron microscopy, the expression of vacuolar-type H ϩ -ATPase was detected along the limiting membranes of pale vacuoles and the ruffled border membranes of odontoclasts. Cathepsin K in odontoclasts was localized within pale vacuoles, lysosomes, the extracellular canals of ruffled borders, and the underlying resorbing dentine surfaces. MMP-9 localization in odontoclasts was similar to those of cathepsin K. RANKL was detected in both mononuclear stromal cells and odontoclasts located on resorbing dentine surfaces. These results suggest that (1) odontoclasts are directly involved in decalcification of apatite crystals by active extrusion of proton ions mediated by H ϩ -ATPase and (2) extracellular degradation of dentine type-I collagen by both cathepsin K and MMP-9, and (3) odontoclast differentiation and activity are regulated, at least in part, by RANKL, possibly produced by mononuclear stromal cells and odontoclasts themselves in the resorbing tissues. Thus, the cellular mechanisms of physiological root resorption appear to be quite similar to those of osteoclastic bone resorption.

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Recent advances in the ultrastructural assessment of osteoclastic resorptive functions

Cited by 24 publications

References 29 publications

Specific biological functions of vacuolar‐type H⁺‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

Specific biological functions of vacuolar‐type H⁺‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

Porcine enamel matrix derivative enhances trabecular bone regeneration during wound healing of injured rat femur

Immunolocalization of vacuolar‐type H⁺‐ATPase, cathepsin K, matrix metalloproteinase‐9, and receptor activator of NFkB ligand in odontoclasts during physiological root resorption of human deciduous teeth

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Recent advances in the ultrastructural assessment of osteoclastic resorptive functions

Cited by 24 publications

References 29 publications

Specific biological functions of vacuolar‐type H+‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

Specific biological functions of vacuolar‐type H+‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

Porcine enamel matrix derivative enhances trabecular bone regeneration during wound healing of injured rat femur

Immunolocalization of vacuolar‐type H+‐ATPase, cathepsin K, matrix metalloproteinase‐9, and receptor activator of NFkB ligand in odontoclasts during physiological root resorption of human deciduous teeth

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Specific biological functions of vacuolar‐type H⁺‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

Specific biological functions of vacuolar‐type H⁺‐ATPase and lysosomal cysteine proteinase, cathepsin K, in osteoclasts

Immunolocalization of vacuolar‐type H⁺‐ATPase, cathepsin K, matrix metalloproteinase‐9, and receptor activator of NFkB ligand in odontoclasts during physiological root resorption of human deciduous teeth