{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:15Z","timestamp":1786977975707,"version":"build-2736575974"},"reference-count":78,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T00:00:00Z","timestamp":1058486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microscopy Res &amp; Technique"],"published-print":{"date-parts":[[2003,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The differentiation and functions of osteoclasts (OC) are regulated by osteoblast\u2010derived factors such as receptor activator of NFKB ligand (RANKL) that stimulates OC formation, and a novel secreted member of the TNF receptor superfamily, osteoprotegerin (OPG), that negatively regulates osteoclastogenesis. In examination of the preosteoclast (pOC) culture, pOCs formed without any additives expressed tartrate\u2010resistant acid phosphatase (TRAP), but showed little resorptive activity. pOC treated with RANKL became TRAP\u2010positive OC, which expressed intense vacuolar\u2010type H\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase and exhibited prominent resorptive activity. Such effects of RANKL on pOC were completely inhibited by addition of OPG. OPG inhibited ruffled border formation in mature OC and reduced their resorptive activity, and also induced apoptosis of some OC. Although OPG administration significantly reduced trabecular bone loss in the femurs of ovariectomized (OVX) mice, the number of TRAP\u2010positive OC in OPG\u2010administered OVX mice was not significantly decreased. Rather, OPG administration caused the disappearance of ruffled borders and decreased H\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase expression in most OC. OPG deficiency causes severe osteoporosis. We also examined RANKL localization and OC induction in periodontal ligament (PDL) during experimental movement of incisors in OPG\u2010deficient mice. Compared to wild\u2010type OPG (+\/+) littermates, after force application, TRAP\u2010positive OC were markedly increased in the PDL and alveolar bone was severely destroyed in OPG\u2010deficient mice. In both wild\u2010type and OPG\u2010deficient mice, RANKL expression in osteoblasts and fibroblasts became stronger by force application. These in vitro and in vivo studies suggest that RANKL and OPG are important regulators of not only the terminal differentiation of OC but also their resorptive function. To determine resorptive functions of OC, we further examined the effects of specific inhibitors of H\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase, bafilomycin A1, and lysosomal cysteine proteinases (cathepsins), E\u201064, on the ultrastructure, expression of these enzymes and resorptive functions of cultured OC. In bafilomycin A1\u2010treated cultures, OC lacked ruffled borders, and H\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase expression and resorptive activity were significantly diminished. E\u201064 treatment did not affect the ultrastructure and the expression of enzyme molecules in OC, but significantly reduced resorption lacuna formation, by inhibition of cathepsin activity. Lastly, we examined the expression of H\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase, cathepsin K, and matrix metalloproteinase\u20109 in odontoclasts (OdC) during physiological root resorption in human deciduous teeth, and found that there were no differences in the expression of these molecules between OC and OdC. RANKL was also detected in stromal cells located on resorbing dentine surfaces. This suggests that there is a common mechanism in cellular resorption of mineralized tissues such as bone and teeth. Microsc. Res. Tech. 61:483\u2013495, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jemt.10370","type":"journal-article","created":{"date-parts":[[2003,7,21]],"date-time":"2003-07-21T06:11:19Z","timestamp":1058767879000},"page":"483-495","source":"Crossref","is-referenced-by-count":122,"title":["Differentiation and functions of osteoclasts and odontoclasts in mineralized tissue 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