{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:43:24Z","timestamp":1784288604037,"version":"3.55.0"},"reference-count":41,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:p>Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-\u03baB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption. Serum concentrations of RANKL are extremely high in OPG-deficient (OPG\u2212\/\u2212) mice, suggesting that circulating RANKL is involved in osteoclastogenesis. RANKL\u2212\/\u2212 mice exhibit osteopetrosis, with the absence of osteoclasts. We examined the requirements for osteoclastogenesis using OPG\u2212\/\u2212 mice, RANKL\u2212\/\u2212 mice, and a system involving bone morphogenetic protein 2 (BMP-2)-induced ectopic bone formation. When collagen disks containing BMP-2 (BMP-2-disks) or vehicle were implanted into OPG\u2212\/\u2212 mice, osteoclast-like cells (OCLs) and alkaline phosphatase-positive OCLs appeared in BMP-2-disks but not the control disks. F4\/80-positive osteoclast precursors were similarly distributed in both BMP-2- and control disks. Cells expressing RANKL were detected in the BMP-2-disks, and the addition of OPG to the disk inhibited OCL formation. Muscle cells in culture differentiated into alkaline phosphatase-positive cells in the presence of BMP-2 and accordingly expressed RANKL mRNA in response to PTH. This suggests that RANKL expressed by osteoblasts is a requirement for osteoclastogenesis. We then examined how osteoblasts are involved in osteoclastogenesis other than RANKL expression, using RANKL\u2212\/\u2212 mice. BMP-2- and control disks were implanted into RANKL\u2212\/\u2212 mice, which were injected with RANKL for 7 d. Many OCLs were observed in the BMP-2-disks and bone tissues but not the control disks. These results suggest that osteoblasts also play important roles in osteoclastogenesis through offering the critical microenvironment for the action of RANKL.<\/jats:p>","DOI":"10.1210\/en.2006-0216","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T00:36:54Z","timestamp":1145579814000},"page":"3366-3374","source":"Crossref","is-referenced-by-count":62,"title":["Osteoblasts Provide a Suitable Microenvironment for the Action of Receptor Activator of Nuclear Factor-\u03baB 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